Diabetes Core Update May 2015 - Diabetes Core Update

Summary5 min read

Diabetes Core Update – May 2015

Podcast Date: April 24, 2015
Hosts: Dr. Neil Skolnik & Dr. John Russell
Theme: “Future World in Diabetes” – Exploring new research on diabetes pathogenesis, early detection, comorbidities, and futuristic therapeutic approaches.

Episode Overview

This episode presents a “Future World in Diabetes,” focusing on innovative studies from ADA journals. Dr. Skolnik and Dr. Russell discuss groundbreaking advances in understanding the etiology, early markers, and treatment strategies for both type 1 and type 2 diabetes. Topics include links between fitness and glycemic control, enteroviral associations with type 1 diabetes, early neuropathy in prediabetes, celiac serology in children, and the potential of reprogrammed gut bacteria as treatment.

Key Discussion Points & Insights

1. Cardiorespiratory Fitness and Glycemic Control

Article from Diabetes Care
[01:56]

Study Summary:
A cohort study (n > 300, heterogenous in age, BMI, glucose control) assessed how VO₂max (cardiorespiratory fitness) correlates to glycemic indices such as A1C and fasting glucose, across the entire spectrum from normal to diabetic.
Findings:
- Low VO₂max correlated closely with poor glycemic control (higher A1C, fasting/2hr glucose levels).
- Both early and late phase glucose-stimulated insulin secretion were worse in those with low VO₂max.
Clinical Correlations:
Dr. Skolnik connects these findings to established trials, emphasizing the pivotal role of physical fitness:

“Poor fitness equates with poor control... one of the core principles that we need to impart to patients is that exercise leads to better sugar control and better health.” — Dr. Neil Skolnik [02:47]
Memorable Reference:
- Cites the DPPT (2002) and Look Ahead trials, which demonstrated lifestyle (exercise + diet) dramatically reduces diabetes progression.

2. Enteroviral Infection and Type 1 Diabetes Etiology

Article from Diabetes
[04:07]

Study Summary:
Researchers examined fresh pancreatic tissue in newly diagnosed adults with type 1 diabetes (3-9 weeks after onset) for enteroviral proteins/RNA.
Findings:
- Enteroviral proteins found in islets in all T1D patients but only in 2 of 9 controls.
- Viral RNA present in most T1D cases, not in controls.
Interpretation & Future Directions:
Dr. Russell discusses the possibility of a viral (enteroviral) cause for T1D long suspected since the 1960s, opening up potential for antivirals or vaccines:

“Could it be possible in a few years that we would be vaccinating all our children with a vaccine against enterovirus… to get rid of type 1 diabetes?” — Dr. John Russell [06:03]
Clinical Implications:
- While no antiviral exists yet, this could transform prevention strategies if confirmed.

3. Peripheral Neuropathy in Prediabetes and Early Diabetes

Article from Diabetes Care (PROMIS cohort)
[07:11]

Study Summary:
Peripheral neuropathy prevalence and nerve dysfunction assessed in 467 adults at high risk for T2D (PROMIS cohort).
Findings:
- Neuropathy present in 29% of normoglycemic, 49% of prediabetic, and 50% of new-onset diabetic subjects.
- Progression toward diabetes over three years increased neuropathy risk.
Clinical Insight:
Dr. Skolnik remarks on how this matches clinical experience, but he notes the surprisingly high prevalence detected (potentially due to sensitive testing tools):

“It can be also an early manifestation of diabetes and in fact present prior to someone’s diagnosis of diabetes...” — Dr. Neil Skolnik [08:51]
Takeaway:
- Consider diabetes or prediabetes as a potential cause in any peripheral neuropathy, even pre-diagnosis.

4. Celiac Serology Fluctuations in Children with Type 1 Diabetes

Article from Diabetes Care
[10:04]

Study Summary:
Longitudinal study of 446 children with T1D, tracking celiac disease serology and its course.
Findings:
- 14% became celiac-serology positive.
- 58% had persistently elevated titers; 41% fluctuated; 28% normalized spontaneously.
Clinical Perspective:
Dr. Russell discusses the reassuring implication—that not all children need a lifelong gluten-free diet:

“Perhaps there’s some hope that we could be able to use wheat products… in some of these children who are going to be struggling to stay away from all the refined sugars and carbohydrates of the world.” — Dr. John Russell [11:34]
Application:
- Recommends retesting and not immediately committing to restrictive diets unless persistent/high titers or symptoms exist.

5. Reprogrammed Bacteria — The Future of Type 2 Diabetes Treatment?

Article from Diabetes
[12:10]

Study Summary:
Researchers engineered Lactobacilli to secrete GLP-1, shown to transform gut epithelial cells into insulin-producing cells in diabetic rats.
Findings:
- Treated rats had higher insulin, better glucose tolerance, and ~25–33% of normal islet capacity restored by gut cell conversion.
Future Impact:
Dr. Skolnik calls these kinds of innovations “awe inspiring,” merging translational medicine with futuristic therapies:

“The amount of potential advancements in the field as evidenced by these two articles this month, are just simply awe inspiring. And it is a fantastic time to be treating patients with diabetes…” — Dr. Neil Skolnik [13:36]
Big Picture:
- Optimism around both understanding T1D’s roots and bioengineered treatments for T2D, emphasizing it’s “the treatments of the future.” [14:32 - Dr. John Russell]

Memorable Quotes

On Exercise and Glycemic Control:

“One of the core principles that we need to impart to patients is that exercise leads to better sugar control and better health.” — Neil Skolnik [02:47]
On Enteroviral Etiology for T1D:

“Could it be possible in a few years that we would be vaccinating all our children… to get rid of type 1 diabetes?” — John Russell [06:03]
On Early Neuropathy:

“It can be also an early manifestation of diabetes and in fact present prior to someone’s diagnosis of diabetes.” — Neil Skolnik [08:51]
On Celiac Serology in T1D:

“Perhaps there’s some hope that we could be able to use wheat products… in some of these children…” — John Russell [11:34]
On Future-Oriented Research:

“The amount of potential advancements in the field... is just simply awe inspiring.” — Neil Skolnik [13:36]

Timestamps for Key Segments

[01:56] – Cardiorespiratory Fitness & Glucose Control
[04:07] – Enteroviral Infections in T1D
[07:11] – Peripheral Neuropathy in High-Risk Patients
[10:04] – Celiac Serology Normalization in Children with T1D
[12:10] – Reprogrammed Bacteria for T2D Treatment
[13:36] – Reflections on “awe inspiring” research & the future

Summary Table

| Segment | Topic | Timestamp | |:--------------------------------------- |:---------------------------------------------------|:---------:| | Cardiorespiratory Fitness & A1C | Fitness links to better glucose control | 01:56 | | Enteroviral Roots in T1D | Evidence for enteroviruses as trigger | 04:07 | | Early Neuropathy Detection | Neuropathy prevalent before diabetes diagnosis | 07:11 | | Celiac Serology Fluctuates in T1D Kids | Not all seropositive children need lifelong GF diet | 10:04 | | GLP-1 Engineer Bacteria Therapy | Future prospect: gut bacteria treat T2D | 12:10 |

Conclusion

This forward-looking episode synthesizes major research trends, emphasizing early detection, preventive strategies, and novel therapeutics, inspiring clinicians with optimism about transformative care options on the horizon for both type 1 and type 2 diabetes.

For further reading: diabetesjournals.org

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Transcript14 lines

[00:04]
A
Welcome to the American Diabetes Association Diabetes Core Update, where we will regularly keep you up to date on the latest clinically relevant articles from the American Diabetes Association's four science and medical journals, Diabetes, Diabetes Care, Clinical Diabetes and Diabetes Spectrum. Joining us for this program are Dr. Neal Skolnick, who is is a professor of Family medicine at Temple University School of Medicine and Associate Director in the Family Medicine Residency Program at Abington Memorial Hospital. Welcome, Dr. Skolnick.
[00:38]
B
Thank you. It's a pleasure to be here.
[00:40]
A
And Dr. John Russell, who is a professor of Family Medicine at Temple University School of Medicine and director in the Family Medicine Residency Program at Abington Memorial Hospital.
[00:50]
C
Thank you. I'm looking forward to going over this week's articles.
[00:53]
A
And now for the articles.
[00:57]
B
We have an incredibly exciting issue this month that we're going to dub Future World in Diabetes because of a couple of the articles that we're going to go over. The first article, plain and simple, is going to be cardiorespiratory fitness and Glucose control from Diabetes Care. But the second article that we're going to talk about is going to go over enteroviral infections and their association with with type 1 diabetes with enormous implications potentially for the Future of type 1 diabetes. Third Article will be from Diabetes Care, discussing peripheral neuropathy occurring early on or even before the development of diabetes. Next from Diabetes Care, positive celiac titers and type 1 diabetes. And finally an article from Diabetes discussing reprogrammed bacteria as potential treatment for type 2 diabetes.
[01:56]
C
Our first article is from Diabetes Care and it looked at the association between cardiorespiratory fitness and the determinants of glycemic control across the entire glucose tolerance continuum, cardiorespiratory fitness, or VO2max is associated with glycemic control. Yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. This cohort study of over 300 subjects that had heterogeneous age, sex, BMI and glycemic control underwent measurements of body composition A1C fasting glucose, oral glucose tolerance test and VO2 max. It was found that a low VO2 max was associated with a high A1C high fasting glucose, a high 2 hour glucose tolerance test and high early and late phase glucose stimulated insulin secretion.
[02:47]
B
Neil John, this study was elegant, simple and straightforward. It really showed the physiologic correlates of something we've seen in a number of clinical studies. It's very clear that across the continuum from prediabetes to early diabetes to late diabetes. Poor fitness equates with poor control. We saw this clinically in the DPPT study, New England Journal, 2002, showing that exercise, along with appropriate diet, decreased progression substantially by 60% from prediabetes on to diabetes. We saw this in the Look Ahead trial that interventions including exercise along with diet decreased a 1Cs. And we're seeing here the physiologic correlates of those clinical decreases. I think we can say unequivocally for wherever our patients are on the continuum from pre diabetes to new or established diabetes, that one of the core principles that we need to impart to patients is that exercise leads to better sugar control and better health. Our next article is from Diabetes and the title is Detection of a Low Grade Enteroviral Infection in the Islets of Langerhans of Living Patients with newly diagnosed type 1 diabetes. The diabetes Virus Detection Study is the first to examine fresh pancreatic tissue at diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed in 3 to 9 weeks after onset of type 1 diabetes in 6 adults aged 24, 35 years of age. The presence of enteroviral capsid proteins and the expression of Class 1 HLA were investigated by immunohistochemistry. Non diabetic organ donors served as controls. Enteroviral capsid protein was detected in the islets of Langerhans of all type 1 diabetic patients and only 2 of 9 controls. Enterovirus specific RNA sequences were detected in 4 of 6 patients and none of the controls. And the authors made sure that the results were confirmed in various laboratories.
[05:22]
C
JOHN so I think when we think about type 2 diabetes and kind of the etiology that we just have to look around, and as the average American has gotten larger, it probably is not a mystery why there's more type 2 diabetes. But type 1 diabetes has always been more enigmatic. And certainly since the late 60s, people have thought potentially that there could be a viral etiology. And certainly there have been other papers that have looked at enteroviruses and thought about enteroviruses as a causative factor, and certainly that would make sense as kind of a random event. And enteroviruses do seem to have a propensity to cause some cellular damage to lead to some of the things that we see in type 1 diabetes. I think the fascinating thing is what would we do with this information if we're 100% sure that enterovirus is the causative agent in this. Well, we could use some treatments, you know, early on, but we really don't have a good antiviral treatment against enterovirus. So perhaps that's something that people could research and see. Can we find something to kind of break this cycle early on when someone presents in ketoacidosis with an initial presentation? More interestingly is, is this something that could be targeted for vaccines? Certainly we've had other vaccines against enteroviruses and as a viral entity it's a relatively simple thing to develop a vaccine against. So could it be possible in a few years that we would be vaccinating all our children with a vaccine against enterovirus in the hopes that we would get rid of type 1 diabetes that we're developing? So stay tuned. Our next article is from Diabetes Care and it looked at peripheral neuropathy and nerve dysfunction in individuals at high risk for type 2 diabetes. The PROMIS cohort. This was a study of 467 individuals that were in the longitudinal PROMIS cohort. Peripheral neuropathy was defined by the Michigan Neuropathy Screening Instrument and the severity of nerve dysfunction was measured objectively by vibration perception thresholds. Metabolic syndrome was defined using the International Diabetes Federation and American Heart association criteria. The prevalence of peripheral neuropathy was 29% in patients with normal glycemia, 49% in pre diabetics and 50% in new onset diabetics, respectively. Additionally, progression of glucose intolerance over three years predicted a higher risk of peripheral neuropathy and nerve dysfunction.
[07:58]
B
Neil John, this study is interesting. There's parts of this study that I really like and confirm what my sense has been for a long time clinically and some parts of the study that surprised me. So what confirms what we see clinically? I think all of us have seen patients who present with puzzling peripheral neuropathies. They have glucoses in that 100 to 125 range. They don't have diagn diabetes, they have prediabetes and we're surprised they have a peripheral neuropathy. Eventually they develop diabetes and over a long period of follow up the only explanation for their peripheral neuropathy is the fact that they have diabetes. We used to think of neuropathy as a consequence of having diabetes for a long period of time, worse when someone's diabetes is out of control. What this study confirms that many of us have seen clinically is that it can be also an early manifestation of diabetes and in fact present prior to someone's diagnosis of diabetes. That's what I like about the study. What do I find surprising about this study? The prevalence of neuropathy here far exceeds that which certainly I see in my patients. When you're talking about patients with prediabetes and diabetes having 40 to 50% rate of peripheral neuropathy, I think the tools that they're using to detect neuropathy probably far exceed the monofilament testing that most of us are doing in the office. I wonder if there's also something to do with the particular population that they looked at. Nonetheless, the take home point here is when seeing patients with prediabetes or seeing anyone with a peripheral neuropathy, think about one of the causes as being related to diabetes, even if that person hasn't been diagnosed yet. The next study from Diabetes Care is titled High rate of spontaneous normalization of Celiac serology in a cohort of 446 children with type 1 diabetes. We know that children with type 1 diabetes have a high rate of celiac disease. This study looked at all children referred from 2002 to 2012 with type 1 diabetes and those children were screened for celiac disease at diabetes onset and at specific intervals afterwards in the presence of high antitransglutaminase titers or clinical symptoms. Children were offered endoscopy and asymptomatic patients with low anti TTG titers were invited to second serologic testing after six months of eating a gluten containing diet. The study included 446 children and of these, 14% became positive for celiac serology, 58% had persistently elevated anti TTG titers and 41% had fluctuating titers. Finally, 28% developed negative titers over time.
[11:06]
C
John so what would the clinical significance of this be to the average doctor in practice? I think a couple of the takeaway points are. One is I think we should think that someone has type 1 diabetes, they have an increased risk developing celiac disease. And I think the the positive thing on that, if that does develop, is not all those folks are going to necessarily continue to have the celiac disease. Certainly it's hard enough, especially in children, to get people to adhere to a diet that is going to be consistent with best practices for someone with type 1 diabetes and we throw celiac disease onto that. I think it's that much harder to feed ourselves, let alone a child. So perhaps there's some hope that we could be able to use wheat products and things like that in some of these children who are going to be struggling to stay away from all the refined sugars and the carbohydrates of the world and our last article is from Diabetes and looked at Engineer commensal bacteria reprogram intestinal cells into glucose responsive insulin secreting cells for the treatment of diabetes an inactive form of GLP1 stimulates conversion of both rat and human intestinal epithelial cells into insulin secreting cells. This study investigated whether oral administration of human commensal bacteria engineered to secrete the GLP one could ameliorate hypoglycemic in a rat model of diabetes. Diabetic rats were fed daily with human lactobacilli engineered to secrete GLP1. The diabetic rats that were fed GLP1 secreting bacteria showed significantly increases in insulin levels and additionally were significantly more glucose tolerant than those fed the parent bacterial strain. The rats developed insulin producing cells within the upper intestine in numbers sufficient to to replace 25 to 33% of the insulin capacity of non diabetic healthy rats.
[13:11]
B
Neil John, the title of this podcast could be Future World. Earlier you discussed the implications of finding enteroviral infections in the pancreases of patients with type 1 diabetes. The potential, if this all pans out to be true, potential for vaccines to perhaps prevent type 1 diabetes. And now in this article we're looking at reprogrammed bacterial cells able to make the intestines secrete GLP1, GLP1 being something that when we were in medical school simply didn't exist. Now we're using GLP1 agonists as injectable medicines with incredible success and people are actually looking at how to reprogram cells to secrete GLP1. The amount of potential advancements in the field as evidenced by these two articles this month, are just simply awe inspiring. And it is a fantastic time to be treating patients with diabetes because of the increasing numbers of medicines available and clearly what we see from today's podcast some of the incredible research being done.
[14:32]
C
Since the treatments of the future.
[14:35]
B
For more information and links to the articles that we discussed in this issue, just go to www.diabetesjournals.org until next week. Keep listening and keep learning. Ra.