An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study

Abstract

OBJECTIVE To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring.

RESEARCH DESIGN AND METHODS In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)–control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes.

RESULTS Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10–2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96–3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73–6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50–3.19).

CONCLUSIONS Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.

Diabetes Care 2020 Dec; 43(12): 3086-3093. https://doi.org/10.2337/dc19-1758

Translation – The earlier you develop diabetes your risk of CVD and coronary death is higher. An if one or both of your parents developed either early onset or late onset diabetes you’re screwed.

COVID-19 and Diabetes, Sub-types of DM2, B Vitamins in Diabetes Incidence and more

This article provides an overview of the clinical evidence on the poorer clinical outcomes of COVID-19 infection in patients with diabetes versus patients without diabetes, including in specific patient populations, such as children, pregnant women, and racial and ethnic minorities.

COVID-19 and Diabetes: A Collision and Collusion of Two Diseases — Diabetes 2020 Oct; dbi200032. https://doi.org/10.2337/dbi20-0032

In the article above the researchers reviewed nearly 90 studies.

Novel diabetes subtype characteristics. Overview of distribution and characteristics of subtypes generated by clustering based on clinical parameters in the Swedish ANDIS cohort.

Type 2 diabetes (T2D) is defined by a single metabolite, glucose, but is increasingly recognized as a highly heterogeneous disease, including individuals with varying clinical characteristics, disease progression, drug response, and risk of complications. Identification of subtypes with differing risk profiles and disease etiologies at diagnosis could open up avenues for personalized medicine and allow clinical resources to be focused to the patients who would be most likely to develop diabetic complications, thereby both improving patient health and reducing costs for the health sector. More homogeneous populations also offer increased power in experimental, genetic, and clinical studies. Clinical parameters are easily available and reflect relevant disease pathways, including the effects of both genetic and environmental exposures. We used six clinical parameters (GAD autoantibodies, age at diabetes onset, HbA1c, BMI, and measures of insulin resistance and insulin secretion) to cluster adult-onset diabetes patients into five subtypes. These subtypes have been robustly reproduced in several populations and associated with different risks of complications, comorbidities, genetics, and response to treatment. Importantly, the group with severe insulin-deficient diabetes (SIDD) had increased risk of retinopathy and neuropathy, whereas the severe insulin-resistant diabetes (SIRD) group had the highest risk for diabetic kidney disease (DKD) and fatty liver, emphasizing the importance of insulin resistance for DKD and hepatosteatosis in T2D. In conclusion, we believe that subclassification using these highly relevant parameters could provide a framework for personalized medicine in diabetes.

Subtypes of Type 2 Diabetes Determined From Clinical Parameters — Diabetes 2020 Oct; 69(10): 2086-2093. https://doi.org/10.2337/dbi20-0001

Not just potential for personalized medicine in the treatment of diabetes but perhaps a framework for better risk stratification and selection in life insurance.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study

RESULTS During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2–5 were 0.85 (0.67–1.08), 0.78 (0.60–1.02), 0.82 (0.62–1.09), and 0.70 (0.51–0.97; Ptrend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (Ptrend < 0.01) and insulin (Ptrend < 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (Ptrend < 0.01).

CONCLUSIONS Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study — Diabetes Care 2020 Oct; 43(10): 2426-2434. https://doi.org/10.2337/dc20-0828

Folate is a B vitamin that occurs naturally in foods such as green leafy vegetables, citrus fruit, and beans. So eat your greens and beans. Taking a supplement can’t hurt either. My multivitamin has plenty of folate.

Metformin Should Not Be Used to Treat Prediabetes

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110–125 vs. 100–109 mg/dL (6.1–6.9 vs. 5.6–6.0 mmol/L) and A1C levels 6.0–6.4% (42–46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes—i.e., those with FPG concentrations of 110–125 mg/dL (6.1–6.9 mmol/L) or A1C levels of 6.0–6.4% (42–46 mmol/mol) or women with a history of gestational diabetes mellitus—should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.

Metformin Should Not Be Used to Treat Prediabetes — Diabetes Care 2020 Sep; 43(9): 1983-1987. https://doi.org/10.2337/dc19-2221

Pass (on) the Chips

Eating Ultraprocessed Foods Tied to Diabetes Risk

Higher intake of ultraprocessed foods (for example, packaged snack foods) is associated with increased risk for type 2 diabetes, according to a prospective study in JAMA Internal Medicine.

Over 100,000 French adults completed a series of 24-hour dietary recall questionnaires over a 2-year period. During a median follow-up of 6 years, roughly 820 participants were diagnosed with type 2 diabetes.

After adjustment for body-mass index, physical activity, and other confounders, participants who ate more ultraprocessed foods were at higher risk for diabetes. In particular, the risk increased by 13% with each 10% increase in the proportion of diet comprising ultraprocessed foods.

The authors note that in previous studies, ultraprocessed foods have been linked to increased risks for cancer, cardiovascular disease, and mortality.

JAMA Internal Medicine article (Free abstract)

Background: Physician’s First Watch coverage of ultraprocessed foods & mortality (Free)

NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright © 2019 Massachusetts Medical Society. All rights reserved.

Junk food = bad.

Fake Burgers = also bad.

Got DM1? Don’t do Pot

Abstract

OBJECTIVE We examined the frequency of diabetic ketoacidosis (DKA) in cannabis users compared with nonusers in the T1D Exchange clinic registry (T1DX).

RESEARCH DESIGN AND METHODS The association between cannabis use by total substance score for cannabis (TSC) and DKA in the past 12 months was examined using a logistic regression model adjusted for potential confounders among adults in the T1DX.

RESULTS Of 932 adults with type 1 diabetes, 61 had a TSC >4, which classified them as moderate cannabis users. Adjusting for sex, age at study visit, and HbA1c, cannabis use was associated with a twofold increase in risk for DKA among adults with type 1 diabetes (odds ratio 2.5 [95% CI 1.0–5.9]).

CONCLUSIONS Cannabis use was associated with an increased risk for DKA among adults in the T1DX. Providers should inform their patients of the potential risk of DKA with cannabis use.

© 2019 by the American Diabetes Association.

Cannabis Use Is Associated With Increased Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Findings From the T1D Exchange Clinic Registry

A Plant-based Diet may Lower type 2 Diabetes Risk

Findings  In this systematic review and meta-analysis of prospective observational studies assessing the association between plant-based dietary patterns and risk of type 2 diabetes among adults, higher adherence to plant-based dietary patterns was associated with a lower risk of type 2 diabetes; this association was strengthened when healthy plant-based foods, such as fruits, vegetables, whole grains, legumes, and nuts, were included in the pattern. Findings were broadly consistent in several prespecified subgroups and in sensitivity analyses.

Take this link to the JAMA Internal Medicine article.

Take this link to the Harvard T.H. Chan press release.

 

Whole grains one of the most important food groups for preventing type 2 diabetes

The proportion who developed type 2 diabetes was lowest in the group which reported the highest wholegrain consumption, and increased for each group which had eaten less wholegrain. In the group with the highest wholegrain intake, the diabetes risk was 34 percent lower for men, and 22 percent lower for women, than in the group with the lowest wholegrain intake.

“It is unusual to be able to investigate such a large range when it comes to how much wholegrain people eat,” says Rikard Landberg. “If you divided American participants into 4 groups, the group that ate the most wholegrain would be the same level as the group that ate the least wholegrain in Denmark. In Europe, Scandinavia eats the most, Spain and Italy the least.”

Additionally, the study was uncommonly large, with 55,000 participants, over a long time span — 15 years.

My source article is here and the study abstract can be found here.

 

A Population-Based Study of the Bidirectional Association Between Obstructive Sleep Apnea and Type 2 Diabetes in Three Prospective U.S. Cohorts

CONCLUSIONS –  OSA is independently associated with an increased risk of diabetes, whereas insulin-treated diabetes is independently associated with a higher risk of OSA, particularly in women. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.

Access the study here.

5 Classifications of Diabetes Proposed

  1. Severe autoimmune diabetes (formerly type 1 diabetes): affected 6% of patients in the derivation cohort; characteristics include early-onset disease, relatively low BMI, and GADA-positive
  2. Severe insulin-deficient diabetes: 18% of patients; GADA-negative but similar to cluster 1; lowest HOMA2-B scores
  3. Severe insulin-resistant diabetes: 15%; higher HOMA2-IR scores
  4. Mild obesity-related diabetes: 22%; obese, but not insulin resistant
  5. Mild age-related diabetes: 39%; older than other clusters, but largely similar to cluster 4

Quoted from  NEJM Journal Watch.