บทถอดความฉบับเต็มของ Type 2 Diabetes: From Genetics to GLP-1s with Sof Andrikopoulos

00:05:17.040 --> 00:05:28.639 So I did a lot of liver metabolism uh and glucaneesis and uh measuring enzymes and doing euglycemic hyperinsulinemic clamps in uh in mice to look at insulin resistance. 00:05:28.800 --> 00:05:39.040 So my first foray and my first sort of exposure to diabetes, type 2 diabetes, was all about insulin resistance. 00:05:39.360 --> 00:06:05.120 Uh, and then I did a postdoc at the University of Washington in Seattle with uh this doyen of diabetes called Daniel Port, who put me together with a young Stephen Khan at the time, and we did bitter cell dysfunction because Dan Port was very much interested in the etiology of type 2 diabetes. 00:06:05.759 --> 00:06:52.240 And it turns out that uh, and we'll we'll probably get to this at some point, it turns out that you can't get hypoglycemia or diabetes without a defect in insulin secretion, irrespective of which type of diabetes you look at, whether it's type 1 or type 2, or gestational diabetes, or any forms of uh maturity on diabetes of the youth, MODI, or any other of the rarer conditions, uh rarer types of diabetes, penicillin dysfunction is the sort of cause of it, or impaired insulin secretion or reduced insulin secretion in a prevailing insulin resistance state, which is type 2 diabetes, is the cause of the hypoglycemia. 00:06:52.720 --> 00:06:53.360 Hmm. 00:06:53.680 --> 00:06:57.519 Yeah, that's really set the foundations for today's topic. 00:06:57.680 --> 00:07:02.800 So, all right, sof, we're gonna start with a segment we call clinical confessions. 00:07:02.959 --> 00:07:11.759 And I want to know what's something about diabetes that you were taught maybe earlier in your career that the evidence has since made you rethink? 00:07:12.240 --> 00:07:12.879 Right. 00:07:13.199 --> 00:07:32.240 So uh my um my PhD thesis says, yeah, the mechanism of hepatic uh glucose overproduction uh in an animal model of non-insulin-dependent diabetes, NIDDM. 00:07:32.720 --> 00:07:37.759 So we used to call type 2 diabetes uh non-insulin dependent, and that's not true. 00:07:37.920 --> 00:07:42.800 And we know that the evidence shows that a lot of people with type 2 diabetes use insulin. 00:07:42.959 --> 00:07:49.759 A lot of uh people with type 2 diabetes require insulin to manage their uh blood glucose levels. 00:07:49.839 --> 00:07:57.519 Uh type 2 diabetes is probably a progressive disease, uh likely a progressive disease where insulin plays an important role. 00:07:57.680 --> 00:08:08.240 So I I would say calling it NIDDM, non-insulin-dependent diabetes mellitus, was uh probably something that now we know is not correct. 00:08:08.399 --> 00:08:20.560 Yeah, and and if I can add, the other thing is, you know, when when I started in diabetes 1989, uh type 2 diabetes was, or NIDDM was an old person's disease, right? 00:08:20.720 --> 00:08:23.680 So we'd say, oh, over the age of 60 or 65. 00:08:23.920 --> 00:08:25.600 And we know that that's not true. 00:08:25.759 --> 00:08:32.240 We know

that people can get type 2 diabetes uh much younger, and we can get type 2 diabetes in our teens. 00:08:32.320 --> 00:08:37.919 You know, there's there's there's reports of uh people very young getting type 2 diabetes. 00:08:38.000 --> 00:08:39.679 Probably those two, I would say. 00:08:40.399 --> 00:08:42.399 Yeah, and look, I have to agree, Soph. 00:08:42.480 --> 00:08:48.320 We still see knittim, and that's how it's generally pronounced, NID DM written everywhere. 00:08:48.559 --> 00:08:50.480 Every wound tells a story. 00:08:50.720 --> 00:08:53.200 But it should never end with someone giving up. 00:08:53.360 --> 00:09:03.679 At Wound Rescue, our master's qualified clinicians provide advanced bedside wound care across Australia, helping restore mobility, independence, and confidence. 00:09:03.840 --> 00:09:09.279 Because healing isn't just closing skin, it's helping people get their lives back. 00:09:09.519 --> 00:09:16.879 Call 1-300-193-195 or visit woundrescue.com.au today. 00:09:17.840 --> 00:09:28.399 So thinking about healthcare providers that might be listening in to this podcast, what would you really like them to stop doing from their next shift? 00:09:29.200 --> 00:09:39.360 Look, I I I think uh, you know, type 2 diabetes is a genetic predisposition to bitter cell failure. 00:09:39.600 --> 00:09:46.559 So I think if we can um understand that you know genetics play a really important role. 00:09:46.799 --> 00:10:03.200 I think if we can if we cannot stigmatize type 2 diabetes, uh I think that would go a very long way in providing uh really good care for the person uh that comes into your clinical practice with type 2 diabetes. 00:10:03.679 --> 00:10:08.480 Yeah, I love that because it's not just all bad diet as we tend to hear about. 00:10:08.639 --> 00:10:10.399 So you're so right, Soph. 00:10:10.799 --> 00:10:12.960 Um look, let's go there then. 00:10:13.120 --> 00:10:22.559 We we talk about insulin resistance all the time, but what's actually happening physiologically when someone develops, say, type 2 diabetes? 00:10:22.960 --> 00:10:23.200 Right. 00:10:23.279 --> 00:10:35.600 So so I think it it's it's um, I guess uh we're gonna make generalizations here, but you know, every person's got their own um journey, their own personal journey. 00:10:35.919 --> 00:10:47.519 But in general, what happens is that uh there's a state of insulin resistance, and perhaps that state of insulin resistance is environmental. 00:10:48.000 --> 00:10:52.720 Uh, and then there is a demand on the beta cell to secrete insulin. 00:10:52.799 --> 00:11:05.919 So there is um a stage where there's hypersecretion of insulin, uh, but because there's a predisposition uh to beta cell failure, that hypersecretion cannot be sustained. 00:11:07.120 --> 00:11:09.519 I I sometimes say the fuse blows. 00:11:09.840 --> 00:11:18.320 So you know your genetic predisposition kicks in and you start secreting less and less insulin and your blood glucose levels rise. 00:11:18.480 --> 00:11:33.120 So the way that I would explain it is that um your insulin resistance brings out and masks your genetic predisposition to diabetes in uh when it comes to type 2 diabetes. 00:11:33.279 --> 00:11:36.320 So insulin resistance is important, yes, of course. 00:11:36.720 --> 00:11:40.480 You cannot get diabetes purely on insulin resistance. 00:11:40.879 --> 00:11:49.519 If if that was true, all of the people with obesity and overweight would have diabetes, and they don't. 00:11:49.840 --> 00:11:55.679 Yeah, in Australia, there's about 33% of the adult population that are living with obesity. 00:11:55.919 --> 00:12:02.320 Uh, the adult population of type 2 does is about 5%. 00:12:03.039 --> 00:12:11.440 So those two numbers would be a lot closer if it was just purely on insulin resistance or bad habits or or diets and so on. 00:12:11.600 --> 00:12:21.600 So clearly, genetic predisposition plays uh uh a significant role, and that predisposition is to losing um beta cell function. 00:12:23.279 --> 00:12:29.039 That that's a good point and a visual for everyone that's listening in to think about, you know, if that was the case. 00:12:29.200 --> 00:12:39.840 So look, um, by the time someone's HBA1C crosses that diagnostic threshold, how long has that disease process potentially been developing then? 00:12:40.240 --> 00:12:41.919 Yes, uh very good question. 00:12:42.000 --> 00:12:45.279 So I'm not sure, and it's not quite clear, yeah. 00:12:45.440 --> 00:12:50.399 With type 1 diabetes, it's it's uh most often very acute. 00:12:50.639 --> 00:12:52.879 Uh person feels very ill. 00:12:53.039 --> 00:13:00.240 Uh they probably haven't had a prolonged period of hypoglycemia or undiagnosed diabetes. 00:13:00.639 --> 00:13:04.080 Um uh with type 2 diabetes, we don't know. 00:13:04.240 --> 00:13:15.120 Um the problem there's you know, there's an estimate there's maybe half a million Australians or maybe more who are undiagnosed with type 2 diabetes today. 00:13:15.200 --> 00:13:27.279 Uh and because they haven't gone to the doctor, because their the symptoms aren't as acute uh uh uh as they are, say, when your glucoses go up to 2025. 00:13:27.600 --> 00:13:35.360 Uh so so people probably are are walking around with higher glucose levels and they don't know it. 00:13:35.519 --> 00:13:36.320 A lot of people. 00:13:37.279 --> 00:13:38.080 I don't know. 00:13:38.240 --> 00:13:40.159 The answer is we don't know. 00:13:40.639 --> 00:13:46.799 So then, based off that, we could potentially be diagnosing type 2 diabetes rather late. 00:13:47.360 --> 00:13:51.360 Yeah, yeah, in certain circumstances, I I think I think that's right. 00:13:51.600 --> 00:14:06.240 Uh many years ago, we did a uh a trial, a screening trial, the pharmacy diabetes screening trial with the pharmacy guild, uh, and it was looking at uh trying to screen the general population. 00:14:06.480 --> 00:14:20.159 And that revealed, if I'm not correct, uh if I'm not mistaken, that

revealed, you know, 1.5% of the general population uh had diabetes and didn't know it. 00:14:20.399 --> 00:14:37.919 There's another study that uh the Austin uh hospital did, the diabetes discovery study, uh they published a number of years ago now, where they screened every single person that came into hospital over the age of 54 for diabetes. 00:14:38.000 --> 00:14:46.639 And they found that about 5% of the people that they screened had undiagnosed diabetes. 00:14:46.879 --> 00:14:53.440 Uh, and you know, about 34% of inpatients uh had diabetes. 00:14:53.759 --> 00:14:59.360 So we can put together programs to actually screen. 00:14:59.519 --> 00:15:14.559 I think we can we can put together uh uh more educational or or um uh uh programs to increase the um importance of getting yourself uh uh regularly checked. 00:15:14.639 --> 00:15:32.960 Uh we can get um um GPs to be a little bit more aware and to say to somebody who comes in for, I don't know, let's just say they come in for the flu injection, have you have you done your uh blood glucose test or just general tests, uh blood tests? 00:15:33.039 --> 00:15:35.039 Let's do one and see how we go. 00:15:36.320 --> 00:15:43.279 Is there anything in the research soft that makes recommendations for how often that kind of testing should be done at the GP? 00:15:43.440 --> 00:15:47.039 Are there any signs and symptoms that clinicians listening should be thinking about? 00:15:47.360 --> 00:15:48.720 Yeah, I I I think so. 00:15:48.799 --> 00:16:01.759 If you if you're thinking about signs and symptoms, you know, we talk about the four T's, which is first uh tiredness, going to the toilet a lot, and losing weight without actually wanting to lose weight. 00:16:01.840 --> 00:16:12.159 Uh, if you've got a family history of of of diabetes, type 2 diabetes, uh, that often uh increases your likelihood of getting diabetes if you're overweight. 00:16:12.240 --> 00:16:23.440 Uh, if you're from um certain ethnic backgrounds where diabetes uh prevalence is high, if you're an Aboriginal Torres Islander person. 00:16:24.320 --> 00:16:32.559 We do have a screening uh tool, it's called the OSD Risk, uh, which is a questionnaire that uh people can fill in. 00:16:32.639 --> 00:16:35.039 I think you can do it even online, fill it in. 00:16:36.000 --> 00:17:05.599 You know, if you're if you're over the age of 40, you know, you should be sort of doing this uh uh on an annual basis, probably, uh, to be able to then pick it up uh and and and pick up if you if you've got hyperglycemia or pre-diabetes, which is probably where you want to sort of act and and act um um accordingly to to try and delay uh or prevent the progression to type 2 diabetes. 00:17:06.480 --> 00:17:14.559 And maybe um let's just touch on say gestational diabetes because it might be your 21-year-olds, not those over the age of 40. 00:17:14.720 --> 00:17:17.119 What what should GPs be thinking about? 00:17:17.279 --> 00:17:22.240 When should they take some diagnostics and maybe are there different side effects for those patients? 00:17:24.319 --> 00:17:27.359 So you've opened up now a huge can of worms. 00:17:27.519 --> 00:17:38.559 So so uh we we've worked with Australasian Diabetes and Pregnancy Society, ADIPS uh recently that have updated their uh GDM screening guidelines. 00:17:38.960 --> 00:18:05.359 Uh we still feel that uh doing an OGDT, an old glucose tolerance test in the second trimester, 20 to 24 weeks of age, to try and identify uh women who uh may have hyperglycemia andor gestational diabetes to then be able to um manage that appropriately. 00:18:05.680 --> 00:18:26.160 There are certain circumstances where uh you would screen earlier if there's uh a high risk, if you've had uh gestational diabetes in a previous pregnancy, if you're from uh certain ethnic backgrounds, you may want to get uh screened at 14 weeks. 00:18:26.400 --> 00:18:33.200 The evidence for screening at 14 weeks is a lot weaker than the evidence to screen at 20 to 24 weeks. 00:18:33.359 --> 00:18:38.000 Uh Haley, a very um dynamic. 00:18:38.079 --> 00:18:41.759 Let's just say, I was gonna say controversial, uh uh bleep that out. 00:18:41.920 --> 00:18:43.759 Not controversial, very dynamic. 00:18:43.839 --> 00:18:59.599 It's a very dynamic field, and I think a very important field because we do know that having gestational diabetes increases your risk of type 2 diabetes in the next 10 years by about, say, 40%, and it also has implications on the baby as well, right? 00:18:59.680 --> 00:19:00.640 So yes. 00:19:01.119 --> 00:19:07.839 Yeah, well, that that certainly opened up a very good can so that others can who are listening in take that information. 00:19:08.079 --> 00:19:12.640 So, look, soft, we're increasingly hearing the term diabetes remission. 00:19:13.119 --> 00:19:15.279 What does remission actually mean? 00:19:15.759 --> 00:19:26.400 Look, uh for me, diabetes remission means uh when your uh HPA1C or your fast or your HBA1C is below 6.5 so uh percent. 00:19:26.559 --> 00:19:39.279 So we diagnose diabetes with a HBA1C, and the HBA1C is uh 6.5 or higher, you've got uh type 2 or diabetes. 00:19:39.440 --> 00:19:44.799 If the the your HPR1C is less than 6.5, then you don't have diabetes. 00:19:44.880 --> 00:19:56.640 So for me, it is about having your HBI1C below 6.5, and you can do that by for me again by any means. 00:19:56.799 --> 00:20:15.920 So you can do it by lifestyle and losing weight, you can do it with pharmacotherapy, you can do it with bariatric metabolic surgery, you can do it whichever way is the right way for you as an individual to get your HPM1C below 6.5. 00:20:16.880 --> 00:20:19.519 And so that's the goal for most patients, right? 00:20:19.599 --> 00:20:23.359 And so that's through lifestyle choices, is that what you're saying? 00:20:23.759 --> 00:20:30.559 Well, it's it should be the goal for people who have uncomplicated diabetes. 00:20:30.799 --> 00:20:35.200 So I think again, we need to

make sure that it's the right person that would manage. 00:20:35.359 --> 00:20:52.319 So if you've got a an elderly person uh who's got multiple uh complications, who is in care, uh uh who um is has other issues, HPL and C of 6.5 may be completely and utterly unrealistic. 00:20:52.640 --> 00:20:54.880 And in actual fact, could be dangerous. 00:20:55.039 --> 00:21:09.680 But I think if you're a young person um where you haven't had diabetes for a very long time, you've got a long uh uh life expectancy, you have uh a much lower burden of complications than it is. 00:21:10.960 --> 00:21:17.200 Um it is reasonable to say let's try and get remission. 00:21:17.839 --> 00:21:18.160 Hmm. 00:21:18.319 --> 00:21:28.160 Okay, so then from what I'm hearing, and correct me if I'm wrong, Soph, it it's become almost synonymous that how we judge diabetes control is through that HBA1C. 00:21:28.240 --> 00:21:32.240 So does HBA1C sometimes give us false reassurance? 00:21:32.640 --> 00:21:33.759 Well, yes, yes. 00:21:33.839 --> 00:21:41.039 Uh HBA1C is a measure of your of your glucose management over the last 12 weeks. 00:21:41.200 --> 00:21:48.480 So it doesn't give you the day to day um variations or fluctuations in in blood glucoses. 00:21:48.799 --> 00:22:00.880 Uh so you may be a person that has a very nice HBI1C of and an acceptable HBA1C of 7.1 or 7.2, and people go, okay, that's That's not too bad. 00:22:00.960 --> 00:22:02.000 That's acceptable. 00:22:02.400 --> 00:22:03.680 It could be a lot worse, of course. 00:22:03.920 --> 00:22:06.400 But you're getting a lot of hypos at night. 00:22:06.480 --> 00:22:08.319 And that's not acceptable, right? 00:22:08.480 --> 00:22:10.240 Or you're going really high. 00:22:10.400 --> 00:22:14.240 You're getting very high sugars after your meal or something, right? 00:22:14.319 --> 00:22:22.559 And again, that's not acceptable because either way, we know that that affects your complications and your risk of complications. 00:22:22.720 --> 00:22:35.359 So HBA1C is not the complete picture, but it's it's a good way to assess um blood glucose management. 00:22:36.640 --> 00:22:44.559 So then, Soph, you and I could have the exact same high HBA1C, the exact same number, but very different glucose profiles. 00:22:44.720 --> 00:22:45.839 We respond differently. 00:22:46.000 --> 00:22:46.799 That's what I'm hearing. 00:22:46.880 --> 00:22:47.039 Yeah. 00:22:47.440 --> 00:22:48.160 Totally correct. 00:22:48.319 --> 00:22:48.799 Absolutely. 00:22:48.960 --> 00:22:54.559 You may have a very flat profile, and I may be going like this up and down and up and down and up and down. 00:22:54.640 --> 00:23:03.200 And my glucose may be varying quite quite uh significantly, and yet our HPA1s are the same at 7.1 or 7.2. 00:23:04.000 --> 00:23:08.240 My situation will be a lot worse than yours because you've got a very flat profile. 00:23:08.319 --> 00:23:11.119 Uh, and my risk of complications will be higher. 00:23:11.279 --> 00:23:17.839

And the fact that I'm hypoing uh a lot is dangerous for all sorts of reasons, right? 00:23:17.920 --> 00:23:18.160 Yeah. 00:23:18.480 --> 00:23:19.039 Yeah. 00:23:19.279 --> 00:23:29.440 And taking that holistic personal approach as well, you might have different disease processes, you might have a different lifestyle of where you live socioeconomically, all of these things play into it. 00:23:29.599 --> 00:23:33.039 So um you mentioned, I think, before CGM. 00:23:33.200 --> 00:23:40.480 Can you tell us about CGM and are technologies such as CGM going to change the way we think about diabetes control? 00:23:41.279 --> 00:23:51.119 Yes, I think continuous glucose monitors are a way that somebody can measure their blood glucose on a continuous manner. 00:23:51.359 --> 00:24:17.359 So you get uh your level of blood glucose um I think every five minutes or or thereabouts, so much more continuously, or much you have a much complete picture of what you're doing and how food uh affects your glucose, how exercise affects your glucose, how fasting affects your glucose, how stress affects your glucose, you know, the the choices that you make affect your glucose. 00:24:17.440 --> 00:24:23.839 So it's a good way to actually make those changes to try and have a more flat profile. 00:24:24.000 --> 00:24:29.279 You can only finger prick your finger, you can only prick your finger so many times, right? 00:24:29.680 --> 00:24:35.279 Whereas a CGM really gives you uh a much more complete picture. 00:24:35.359 --> 00:24:43.599 I I sort of liken it to uh going to a room and your finger pricking is looking through the keyhole. 00:24:43.680 --> 00:24:49.680 Uh, whereas your CGM is you've and you can only see with through the keyhole, you can only see a certain amount of the room. 00:24:49.759 --> 00:24:54.880 Uh whereas with your CGM, you've opened the door and you can see the comp the hole in the complete room. 00:24:55.279 --> 00:25:02.720 Yeah, and look, we use those continuous glucose monitoring monitoring now a lot for our type one diabetic management. 00:25:02.880 --> 00:25:06.240 Um, what is there a role maybe for type two as well? 00:25:06.640 --> 00:25:07.440 There certainly is. 00:25:07.519 --> 00:25:14.880 So in Australia, uh uh CGM, continuous glucose monitors are subsidized uh for people with type 1 diabetes. 00:25:15.039 --> 00:25:22.799 We don't have a subsidization for people with type 2, but we are advocating, and I I am optimistic. 00:25:22.960 --> 00:25:31.599 Uh I am uh positively optimistic that we will get subsidization for people with type 2 diabetes, particularly if they're on insulin. 00:25:31.759 --> 00:25:40.880 Uh, and I think you know, people who are using insulin to manage their blood glucose levels should have access to subsidized uh CGM. 00:25:40.960 --> 00:26:06.400 The evidence is very uh clear that you'll get much better uh blood glucose management and you will prevent hypoglycemia, you will prevent DKA, which is the other side, you

will prevent hospitalizations for the people who are using insulin, whether you're type 1 or type 2, to manage your diabetes uh where the risk of hypose is significantly elevated. 00:26:07.440 --> 00:26:09.119 It's real-time care, right? 00:26:09.279 --> 00:26:15.039 So, you know, what I see in front of me makes me stop, think, reevaluate, and change my my own actions. 00:26:15.119 --> 00:26:16.319 So it's important. 00:26:16.480 --> 00:26:29.839 Um, look, Soph, we can't have a conversation about modern diabetes, diabetic care without talking about these GLP1 receptor agonists and the newer therapies coming to fruition very quickly. 00:26:30.079 --> 00:26:37.359 Have these medications fundamentally changed type 2 diabetes in terms of management? 00:26:38.480 --> 00:26:39.039 Totally. 00:26:39.359 --> 00:26:50.480 I think we're in a an absolutely exciting uh uh disease modifying time. 00:26:50.960 --> 00:27:00.480 I think the GLP1 based therapies are at the moment revolutionizing the management of type 2 diabetes. 00:27:01.119 --> 00:27:08.400 Um we've got uh one agent that's been subsidized for type 2 diabetes in Australia. 00:27:08.559 --> 00:27:22.000 There's a second uh dual agonist that's sort of in the mix and trying to get subsidization, and then there's I don't know, a hundred others uh coming. 00:27:22.400 --> 00:27:33.920 Uh injectables, orals, peptides, uh non-peptide synthetics, uh, dual agonist, uh triple agonists, quadruple agonists, you name it. 00:27:34.079 --> 00:27:35.119 It's coming. 00:27:35.279 --> 00:27:48.160 Uh, and you know, I'm going to the European uh diabetes meeting in Milan in a couple of weeks, and I don't know, maybe half the program is about these new GLP1-based therapies. 00:27:48.400 --> 00:28:21.200 They will completely revolutionize uh, or they are, I should say they are revolution revolutionizing type 2 diabetes management and obesity, not only because they cause weight loss and better blood glucose management, but they've shown to protect your heart, you protect your kidney, um, they reduce sleep apnea, they reduce fatty liver disease, they reduce uh chronic pain, uh, you know, peripheral artery disease. 00:28:21.440 --> 00:28:31.359 So there's uh a study called Stride where uh a GLP1 um agonist has been shown to improve uh peripheral artery disease. 00:28:31.440 --> 00:28:33.119 I mean, you know, wow. 00:28:33.519 --> 00:28:34.880 Wow, wow, wow. 00:28:35.279 --> 00:28:36.160 That's all I can say to that. 00:28:39.759 --> 00:28:55.599 I was even reading a recent study about um addiction and how, because of the process that these GLP ones are having on the hippocampus of the brain and how it's lowering the inhibition to even um, you know, drink alcohol or gamble. 00:28:55.759 --> 00:28:58.880 Like this is revolutionary, you know, we've entered a different world. 00:28:59.039 --> 00:29:00.160 And I agree, Soph. 00:29:00.240 --> 00:29:10.240 I was recently at a health ed conference and there was like 2,000 GPs and all of the trade area, every second second trade setup was a GLP one company. 00:29:10.720 --> 00:29:11.119 That's right. 00:29:12.960 --> 00:29:16.640 I mean, I think for us invented Yeah, totally. 00:29:16.720 --> 00:29:27.279 I think for us and and for primary care and secondary care, at some point we're gonna have to figure out um where uh these agents fit. 00:29:27.519 --> 00:29:28.880 How are we going to use them? 00:29:29.039 --> 00:29:33.519 Are we going to use them for blood glucose diabetes management uh primarily? 00:29:33.599 --> 00:29:35.599 Are we using them for weight loss primarily? 00:29:35.839 --> 00:29:38.799 Are we using them to reduce uh PAD? 00:29:39.039 --> 00:29:41.839 Are we using them to reduce fatty liver disease? 00:29:41.920 --> 00:29:49.440 Uh how, you know, or uh yeah, it's gonna be weight and fatty liver, or weight and peripheral artery disease. 00:29:49.519 --> 00:30:00.960 I mean, we're just gonna have to think about um the way that we position these uh therapies because they are truly life-changing therapies. 00:30:01.920 --> 00:30:07.519 So then on that note, does anything concern you about the way they're currently being used? 00:30:08.160 --> 00:30:22.160 Uh no, I I think uh we we in Australia, because we've got um the the PBS, uh we've got at least one uh um option on the PBS. 00:30:22.559 --> 00:30:29.440 Uh one we've got a couple, but one option that probably is is is a very good option. 00:30:29.599 --> 00:30:33.279 I think we need to think about uh more options. 00:30:33.359 --> 00:30:34.880 We need to give people more options. 00:30:34.960 --> 00:30:44.799 So I so I would be encouraging the government to be subsidizing more than just the one uh or couple of uh medications that we have on the on the PBS. 00:30:44.960 --> 00:30:54.160 I I think then we need to uh ensure that uh healthcare professionals are um educated, upskilled about using them. 00:30:54.319 --> 00:31:17.519 You know, there are some um there are some side effects, yeah, gastrointestinal mostly, um, and how to manage gastrointestinal side effects, you know, um timing of meals, maybe smaller meals, the type of foods uh that may be giving you that uh yucky feeling uh in the stomach. 00:31:17.759 --> 00:31:22.640 Um but I but I'm I'm not terribly worried about the use of them. 00:31:22.799 --> 00:31:26.720 Uh there's a fair bit of off-label use in Australia as well. 00:31:26.880 --> 00:31:43.119 Uh and that's appropriate, I think, because they are such powerful uh medications, they should be used for uh you know obesity, they should be used for obesity-related complications, absolutely, because they are changing people's lives. 00:31:43.759 --> 00:31:44.160 Yeah. 00:31:44.799 --> 00:31:49.680 I I think almost every second person's on one now, if I think about the patients that we're seeing. 00:31:49.839 --> 00:31:55.119 And one big thing that stands out for me is the muscle wastage, the changes to bone structure. 00:31:55.279 -->

00:31:59.119 But it comes down, no medication comes without side effects. 00:31:59.200 --> 00:32:01.359 So know the side effects and manage accordingly. 00:32:01.440 --> 00:32:10.960 And I'm always saying to patients time to refer to a dietitian and get their input into good food choices for protein and other macronutrients. 00:32:11.359 --> 00:32:13.440 Dietitian exercise physiologist. 00:32:13.599 --> 00:32:32.000 So uh I tell people that a lot of these side effects are side effects of weight loss, and that weight loss could be through sort of dietary means, it could be through bariatric surgery, it could be through uh uh medications like these GLP ones. 00:32:32.160 --> 00:32:42.880 So this relative uh lean mass loss or muscle mass loss uh will be uh the same as if you had bariatric surgery to lose your weight. 00:32:43.039 --> 00:32:46.400 So then what you need to do and think about is diet. 00:32:46.559 --> 00:32:49.200 Am I having the appropriate nutrition? 00:32:49.359 --> 00:32:54.799 Am I having enough protein to maintain uh my uh my muscle mass? 00:32:54.880 --> 00:33:03.839 And then am I doing my strength exercises, which helps, as you know, with both your bones and and your strength, your muscle strength. 00:33:04.000 --> 00:33:12.559 I think mass is one thing, but I I think it's uh more important is actually strength, muscle strength will be more important. 00:33:13.279 --> 00:33:26.720 And we're not saying get out there and start lifting 100 kilo weights, it's more resistance training and getting the bone a bit of resistance and the muscle so that it keeps building muscle memory and healing in that capacity or growing the muscle. 00:33:26.880 --> 00:33:29.680 Um, I stand with you around advocacy soft. 00:33:30.000 --> 00:33:40.720 We need to advocate to our government and the world to lower the cost of some of these drugs because another reality is we're seeing a lot on the black market and they are unregulated. 00:33:41.039 --> 00:33:44.160 We don't know what people are getting access to or what they're even taking. 00:33:44.240 --> 00:33:45.920 So we'd caution against that. 00:33:46.000 --> 00:33:47.039 I think you would agree. 00:33:47.519 --> 00:33:58.400 I totally, you know, I um uh the the car wash guy uh last week was telling me uh he's on RETA, RETA Trute, and I go to him, how's that work? 00:33:58.559 --> 00:34:00.880 You know, it's not available, it's still experimental. 00:34:00.960 --> 00:34:03.200 I don't even think it's available anywhere in the world. 00:34:03.279 --> 00:34:06.720 He goes, Ah, no, no, man, I'm getting it off the internet. 00:34:06.799 --> 00:34:08.559 And it's like, okay. 00:34:09.039 --> 00:34:10.239 Uh are you sure? 00:34:10.400 --> 00:34:19.760 So, yes, there are people that are buying something, and we don't know what that is exactly, uh from the internet. 00:34:20.159 --> 00:34:23.360 I would caution anybody from doing that. 00:34:23.679 --> 00:34:32.079 Um, be careful, uh, be mindful that you don't exactly know what you're getting and what's in the actual um components of it. 00:34:32.159 --> 00:34:35.360 Yeah, components of it, whatever it is. 00:34:35.440 --> 00:34:44.719 Uh uh, I I think you know you're you're increasing the risk of doing something more harmful to yourself than than benefit. 00:34:44.880 --> 00:34:46.800 Uh uh please be careful. 00:34:46.880 --> 00:34:48.559 Please, please uh don't do that. 00:34:48.719 --> 00:34:50.480 Just please don't just don't do it. 00:34:50.639 --> 00:34:51.440 Don't do it. 00:34:51.920 --> 00:34:53.280 Do it the proper way. 00:34:53.440 --> 00:34:57.679 I mean, a lot of them haven't even reached clinical trials these ones on the black market. 00:34:57.760 --> 00:35:00.400 They're still testing on rats, everybody listening in. 00:35:00.639 --> 00:35:02.880 So stay away from them. 00:35:03.599 --> 00:35:10.400 I mean, there's nothing wrong with rats and testing on rats and mice, but but you actually don't know what's in them. 00:35:10.559 --> 00:35:13.599 You you know, at the end of the day, you don't know what you're getting. 00:35:13.679 --> 00:35:17.519 And I think that that's that's um you're taking a risk. 00:35:17.760 --> 00:35:20.159 And is it worth taking the risk? 00:35:20.320 --> 00:35:21.679 Uh uh no. 00:35:22.400 --> 00:35:24.880 In my opinion, no, it's not worth taking that risk. 00:35:25.599 --> 00:35:28.880 I I think what it comes down to, Soph, is people are desperate. 00:35:29.119 --> 00:35:38.960 And not everyone can afford the the crazy prices that these are$500 or more or more, up to$700 and or even$800 a month for these drugs. 00:35:39.039 --> 00:35:45.840 And so they're desperate, but the long-term effects that you may not feel straight away are absolutely not worth it for your overall health. 00:35:46.000 --> 00:35:47.679 So that's what Sof's alluding to. 00:35:48.000 --> 00:35:50.719 Yeah, and I think uh I think Haley, you're right. 00:35:50.800 --> 00:36:00.559 I think we need to advocate, we need to all get together and advocate for governments to make them cheaper and to make them uh more uh readily available. 00:36:00.639 --> 00:36:04.000 Uh yeah, affordability, access and affordability. 00:36:04.559 --> 00:36:16.639 I could go on about the advocacy space because I don't even know if it's our government, it's more the pharmaceutical companies that have a role here to help the general population who these drugs are life-changing. 00:36:16.719 --> 00:36:27.599 Um, and there is that global war of if Australia drops the price, then we can't compete because other countries will want it lower, and then we lose our return on investment. 00:36:27.760 --> 00:36:30.000 Well, there's a health economics here. 00:36:30.079 --> 00:36:31.280 There's people at the end of the line. 00:36:31.360 --> 00:36:35.280 So that's my two cents worth to any pharma companies listening in. 00:36:36.559 --> 00:36:40.159 So, all right, let's bring this back to wounds soft. 00:36:40.400 -->

00:36:42.880 This is the area that I play in every day. 00:36:43.039 --> 00:36:50.400 What is it about diabetes that makes someone more vulnerable to developing a wound and having difficulty healing it? 00:36:50.880 --> 00:36:56.800 Yeah, it's it's a it's you know, as you know, it's a very um uh important question to ask. 00:36:56.960 --> 00:37:06.960 And I think the hypoglycemia plays a role uh in peripheral vascular disease, it plays a uh a role in in uh peripheral neuropathy. 00:37:07.280 --> 00:37:26.000 Uh and uh I think uh those two in combination then uh increase the propensity to uh somebody having with diabetes having uh uh a wound, and then that wound not being able to heal as quickly or as efficiently as it could. 00:37:26.480 --> 00:37:47.679 Uh I think uh in the first instance uh management of diabetes is important, that's one thing, and then the second thing is uh to always monitor and to always look at your feet and to always uh seek help advice before you develop uh a wound or before that wound gets gets infected. 00:37:47.760 --> 00:37:49.599 So a little bit more preventative. 00:37:50.239 --> 00:38:08.719 I tell people, irrespective of who they are, and I can tell you a friend of mine um a couple of weeks ago, uh, we caught up and said to me that his daughter, the 11-year-old daughter, got diagnosed with typon diabetes, um, which is fine, there's nothing you know, it happens, nothing unusual about that. 00:38:09.360 --> 00:38:13.119 They're getting great care at my shelf, which is wonderful. 00:38:13.280 --> 00:38:15.280 Uh and I'm really pleased. 00:38:15.440 --> 00:38:30.159 But one thing that I said to him is make sure your daughter does not walk barefoot, make sure your daughter always wears proper shoes, make sure your daughter always is wearing something when she's walking outside, particularly when it's hot, as you know, uh all that stuff. 00:38:31.199 --> 00:38:47.039 Not because she's gonna get a winter day tomorrow, but to get into those habits, to get into those good habits early on, uh, to make sure that we we sort of uh prevent anything that that happens uh um later on. 00:38:47.360 --> 00:39:02.079 Uh I think that, and I think then uh I think we need to sort of um empower, engage our uh GPs to when they see a person with type 2 diabetes, they also ask about their feet. 00:39:03.519 --> 00:39:05.360 Really sound information there. 00:39:05.440 --> 00:39:07.039 I like the habit forming actually. 00:39:07.119 --> 00:39:18.079 You've made me think about ways I could even alter some of my discussions with younger patients because they might not have neuropathy today, but it is a high prevalence for patients with diabetes. 00:39:18.239 --> 00:39:19.760 So it makes sense. 00:39:20.719 --> 00:39:26.719 And and there's nothing lost by saying, you know, just wear sandals or wear proper fitting shoes. 00:39:26.800 --> 00:39:29.760 Uh don't walk around bedfoot, basically. 00:39:29.840 --> 00:39:31.119 Yeah, please don't do that. 00:39:31.440 --> 00:39:32.559 Please be careful. 00:39:32.639 --> 00:39:40.719 I mean, you know, you're at home, the kids, they'll run around, you know, whatever, but just sort of try and get in that in in into that into that habit. 00:39:40.880 --> 00:39:42.960 I think we can go a long way. 00:39:43.360 --> 00:39:49.519 You know, you know, there's 6,600 amputations in Australia due to diabetes every year. 00:39:49.679 --> 00:39:57.119 And I think, you know, as we say uh through diabetes feed Australia, that most of those, if not all of those, are preventable, right? 00:39:57.360 --> 00:40:02.400 So so let's just get in the habit of trying to prevent those. 00:40:02.559 --> 00:40:09.679 Beyond that, I think, as I said, I think good uh blood glucose management and then making sure that you're getting your checks. 00:40:09.840 --> 00:40:19.199 Get your get your feet checked, get your um uh uh your um arterial um pulses checked. 00:40:19.360 --> 00:40:24.480 Uh I'm making uh I'm not making sense now, but you you can you can fill in the gaps, Haley, for me. 00:40:24.639 --> 00:40:25.280 Get your pulses checked. 00:40:25.440 --> 00:40:28.400 Yeah, you are you are through your Doppler, Doppler ultrasounds for sure. 00:40:28.639 --> 00:40:34.800 Doppler ultrasound and get your your uh thingos checked with the um uh uh with with the filaments. 00:40:36.159 --> 00:40:39.920 Oh the fil the microfilaments, the microfilament checking for the neuropathy, yes. 00:40:42.239 --> 00:40:44.159 Um totally making sense. 00:40:44.400 --> 00:40:48.719 Um if I think about uh a lot of the patients I have, right? 00:40:48.880 --> 00:40:53.679 Once someone already has a wound, how much does glucose control actually matter? 00:40:53.760 --> 00:40:55.360 And I'm gonna give you an example. 00:40:55.599 --> 00:41:12.079 So many of my patients will say, Oh, I'm sitting at 8.5, I've been sitting at 8.5 for a whole year, but it's just been the last month that they've had a wound and they still consider that's okay because that's what they've normally had as in an elevated um sugar level, but now they have a wound. 00:41:12.239 --> 00:41:16.639 So how much does glucose control actually matter for someone with a wound? 00:41:16.960 --> 00:41:18.880 Yeah, it's a it's a it's a very good question. 00:41:18.960 --> 00:41:21.599 It's a question that I that I ask a lot of people. 00:41:21.760 --> 00:41:41.679 You know, once you get a wound, yeah, how much does uh diabetes matter versus treating the actual wound itself and getting that um de bright and getting that cleaned and getting that uh with with the appropriate medications and antibiotics and so on. 00:41:42.800 --> 00:41:45.360 My feeling is that diabetes still matters. 00:41:45.440 --> 00:41:53.440 My my feeling is that if you can continue to manage your your blood glucose levels well, then that cannot hurt, right? 00:41:53.519 --> 00:42:14.000 That that that would obviously have some sort of benefit, even if you have

peripheral neuropathy, even if you have uh uh a wound uh that requires attention, I would think that managing blood glucose levels would still make some sort of difference and would still be of benefit. 00:42:14.239 --> 00:42:17.199 You know, bugs love sugar. 00:42:17.440 --> 00:42:24.639 Uh and so we can probably do well by not having uh sugar for those bugs to love. 00:42:25.280 --> 00:42:30.400 So so uh I would think that that it's probably um very important. 00:42:32.400 --> 00:42:38.400 All right, well, you've been also heavily involved in this great program called the Foot Forward Program. 00:42:38.719 --> 00:42:40.880 What can you tell our listeners about it? 00:42:41.199 --> 00:42:56.000 So the foot forward program is funded by the National Diabetes Services Scheme, which is a Department of Health, a federal government uh scheme uh that Diabetes Australia manages on behalf of uh the uh government. 00:42:56.159 --> 00:43:00.079 There's a number of components that so sorry, so I should go back a step back. 00:43:00.159 --> 00:43:02.480 Uh there's two components to Foot Forward. 00:43:02.639 --> 00:43:07.760 There's a um lived experience or consumer component, and then there's the health professional component. 00:43:07.840 --> 00:43:14.559 And within the health professional component, there's a number of uh resources or a number of activities that we've done. 00:43:14.639 --> 00:43:21.920 Uh one of them is about uh pathways and integrated pathways, and there's uh there's two main pathways. 00:43:22.000 --> 00:43:29.440 There's the management pathway, and then there's the prevention pathway, and they're color-coded, and they're really, really good. 00:43:29.679 --> 00:43:34.480 Uh, footforward.org org.au if you want to get the resources. 00:43:34.639 --> 00:43:36.559 And then there's an educational component. 00:43:36.639 --> 00:43:59.360 So we've put together uh educational modules uh for nurses, for podiatrists, for aboriginal and Torres Island health workers, uh uh, which takes you through everything that we talked about today about um screening, diagnosis, what the peripheral neuropathy is, what peripheral arterial disease is, uh, how to manage it, how to test for it. 00:43:59.519 --> 00:44:26.079 Um the LOPS, the the um angle um um um uh pulses uh excellent uh outstanding uh um educational modules that it you can do and they're for free uh and they're available um for everybody to do uh and then there's webinars and then there's uh other resources on the website that you can uh access. 00:44:26.480 --> 00:44:28.639 Um uh I'm biased. 00:44:28.880 --> 00:44:37.440 Uh yeah Natalie we should put this together on behalf of the ADS um uh I think she's done an outstanding job. 00:44:37.599 --> 00:44:43.199 Uh I think they're really great resources and I think we should be um uh trying to implement them. 00:44:43.360 --> 00:45:47.039 The other um uh component to Foot Forward is train the trainer so you can get resources by which you can then train local health uh workers um uh to be able to screen and manage uh diabetes-related foot disease and I would encourage that that's that was put together uh specifically for um rural remote uh communities and and health services where getting specialist care may not be as accessible as possible you can get the train the trainer um uh resources to be able to then uh apply upskill your your local um health uh workers to to to be able to manage people in that community i've I've actually personally had a look at the resources and they are phenomenal there is so much information there we will put into the show notes uh the link of where you can go to to access those resources and I highly encourage everybody listening in to get over there and have a look because it's brilliant. 00:45:47.199 --> 00:45:52.159 So well done Soph and and the team and your colleagues for putting that all together. 00:45:52.960 --> 00:45:57.679 Soph, I want to get into what this uh podcast is really about and that's the controversial question. 00:45:57.760 --> 00:46:15.760 So I'm gonna kick it off with asking is calling type 2 diabetes a lifestyle disease scientifically inaccurate and potentially harmful yes it's inaccurate and harmful because it stigmatizes people. 00:46:16.159 --> 00:48:06.400 Type 2 diabetes is a disease of the beta cell not secreting enough insulin the appropriate amount of insulin for the prevailing insulin resistance and the insulin resistance is likely to be lifestyle so can you improve things by uh um putting uh in place lifestyle measures yes you can uh but uh type2 diabetes is a better cell dysfunction disease which is caused by your genetics yeah absolutely so are then clinicians here's the next question too focused on HBA1C uh no I think we are focused on HBA1C I think uh perhaps um uh um yeah I was gonna I'm gonna say appropriately uh on HBA1C but we can do better now with that we've got CGM we can do better we can get better uh measures of uh blood glucose management so I would say HPI1C is still very very relevant and important in type 2 diabetes and in type 1 diabetes but I think we can get much more nuanced much more granular information if we use CGM and make uh specific changes to people's uh management of the diabetes which probably it would be a lot more effective all right then perhaps one of the biggest questions that comes to mind with all the medications the technology that's out there we've spoken about some guidelines that are available you've mentioned how many you're involved with and the knowledge we have why are people still developing these complications and type 2 diabetes besides the genetics component because we don't know the underlying cause of disease and the drugs that we have do not treat the underlying cause of disease. 00:48:06.559 --> 00:48:16.800 Even the GLP1 based therapies which we've just spoken about do not treat the underlying cause of disease because we honestly do not know what it is. 00:48:16.960 -->

00:48:27.519 So for me the way that I look at the management of diabetes even today with these wonderful drugs that we have is that they are band-aid measures. 00:48:27.840 --> 00:48:52.400 They don't treat the underlying cause of disease can we um they're not durable in other words they're not durable so yes you're gonna get good glycemic management for a period of time and things will look well for a period of time but it is a progressive disease and blood glucose levels do increase at certain times and you do get you do need more and more medication. 00:48:52.480 --> 00:53:19.280 So that's why we still have complications all right let's look to the future then the Australian Diabetes Society is involved in the national diabetes research strategy for 2026 to 2035 what are the big questions we still need diabetes research to answer in your opinion well I I I think um yeah what causes uh type 1 diabetes uh what causes type 2 diabetes um uh why do some people develop complications while other people may not develop as severe complications um uh what are the interventions that we can put in place that are sustainable and that are of benefit uh we've spoken a little bit about lifestyle okay uh what's the appropriate lifestyle uh what's the appropriate diet we still don't know uh whether um you know I'm I'm gonna be again controversial given this is the controversial part we still don't know whether a low carb high fat diet is the right diet for diabetes uh it probably suits some people it may not suit other people and I've gotten uh into trouble in the past for saying these uh making these comments I don't think um uh we should uh completely eliminate uh carbs from a diet I would uh encourage people to um seek uh advice uh get a um an accredited uh dietitian uh to to help you with your diabetes uh management and your lifestyle and your and your uh dietary um requirements uh I think you know how does insulin resistance uh influence beta cell failure we still don't know that why does the immune system um attack the beta cells and kills kill the beta cells in type 1 diabetes we still don't know the answer to that uh are uh in type 1 diabetes we now have uh immune modulatory therapies that can um delay the onset of type 1 diabetes for a little bit of time can we really really delay type 1 can we prevent type 1 diabetes uh can we prevent type 2 diabetes uh um uh I think these are questions that that yeah are really really important uh you know what what causes beta cell dysfunction can we can we uh target that cause with an intervention to be able to then preserve beta cell function mass to to make management of types of diabetes better uh easier so so many questions still to be answered so for all the years you've been working in the field so many to go you know and I all of the research that I've read and I am not a dietitian I'd agree with sof consult a dietitian but everything always leads back to the Mediterranean diet so you know I think there's something in that sof us Greeks you know we we peaked two and a half thousand years ago but we're still we're on the way back now and and it always goes back to the Greeks as well so back to the Greeks of course uh and feta cheese and tzatziki uh uh you know and and tomatoes you know olives you know you can't you can't go you can't go wrong you know you can't go wrong I have to agree give me a word and I can tell you how it's come from the Greeks give me a word I know I know that's true we could do a whole other podcast on that stuff I love it so I have one final question for you look you've spent your career looking at diabetes from the laboratories laboratory to research to clinical care now at a national policy level so if every healthcare professional listening in could change one thing tomorrow that would generally reduce the future burden of diabetes and its complications what would you want them to focus on uh when you diagnose a person with diabetes whichever form of diabetes it is please manage them in a more proactive manner I was gonna say aggressive but in a more proactive manner. 00:53:19.519 --> 00:53:34.079 We know from all the trials that the the better management of diabetes particularly early on the more likely you're going to reduce the risk of complications later in the disease process. 00:53:34.239 --> 00:54:22.239 So the one thing that I would say would be to be proactive and manage the people's diabetes as effectively and efficiently as possible try and normalize uh or try and reduce blood glucose HBA1Cs as much as you possibly can at that early stage be proactive well yes totally agree just do it just do it you've heard it here first just do it I agree with you all right so a wound is never just a wound it's the walk that never happened the grandchild that couldn't chase the confidence they slowly lost at wound rescue we see more than the wound. 00:54:22.400 --> 00:54:54.719 We bring advanced wound care directly to homes, aged care, general practice and communities across Australia because we're healing lives not just wounds call 1300 19315 or visit woundrescue.com.au today we're going to finish with uh a segment we call rapid fire this is where we get to unwrap whether something is true or false but the kicker here soft is there's no time to elaborate you have to think quick and it's about having a bit of fun. 00:54:54.880 --> 00:56:25.760 How does that sound uh I'm all for fun all right let's kick it off true or false type two diabetes is primarily a lifestyle disease false genetics plays an important role in someone's risk of developing type 2 diabetes very true a good HBA1c always means someone's diabetes is well controlled false everyone with type 2 diabetes should be using a CGM true yeah true type 2 diabetes can go into remission true losing weight automatically cures type 2 diabetes false false technology false false false technology alone will solve Australia's diabetes problem false and finally we should be optimistic about the future of diabetes care uh a hundred percent true uh no doubts in that absolutely true thank you soft thank you so much for joining us it's been fascinating to take the conversation beyond diabetes complications and really understand the disease behind them I think your ability to bring together the science the research and the bigger picture of diabetes care has given us all something to think about. 00:56:26.159 --> 00:56:40.000 I want to thank you for sharing your knowledge your time with us and for continuing to do what you are doing to shape diabetes in um in in Australia it's been an absolute pleasure with having you on Wundcare Unwrapped. 00:56:40.559 --> 00:57:25.360 Thank you thank you Haley thank you for the opportunity thank you for having me thank you for for um addressing to me a very important topic you know there's 1.5 million people with uh diabetes in Australia all forms of diabetes probably more with the undiagnosed people I think it's an important topic so thank you for uh shining the light uh uh on diabetes and for giving me the opportunity to to discuss it with you thanks so much Soph thank you for tuning in to this episode of woundcare unwrapped you can find us on LinkedIn Facebook Instagram and TikTok at wound rescue pty ltd a big thank you to our show partners at Learn on the move you can find more about them in our show notes. 00:57:25.519 --> 00:57:33.920 Now woundcare changes when we start having real conversations and that's why we believe it's about healing lives and not just wounds. 00:57:34.079 --> 00:57:38.239 Tune in for next week's episode of Woundcare Unwrapped