Targeting Cell Aging May Yield Diabetes Therapy

Targeting how cells age may one day provide a significant therapy to prevent and treat type 2 diabetes mellitus (DM) and its complications. When patients with DM eat carbohydrates, not how much, may help them lower postprandial glucose and insulin levels. The heart muscle damage seen in DM may be a result of how a sugar and its enzyme affect muscle contractions. A genetic predisposition to obesity appears to raise the risk of type 2 DM.

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Cellular Senescence Offers Target to Prevent Complications

• Cellular senescence, which has been implicated in several age-related diseases, is a fundamental aging mechanism that may play a role in the pathogenesis of type 2 DM through a direct effect on pancreatic β-cell function, senescence-associated secretory phenotype-mediated tissue damage, and involvement in adipose tissue dysfunction.

• Metabolic and signaling changes seen in DM can promote the formation of senescent cells.

• Senescent cells might be part of a pathogenic loop in DM-both a cause and a consequence of metabolic changes and tissue damage.

•Therapeutic targeting of cellular senescence may have a large impact on the pathogenesis of DM and could prevent complications better than currently available therapies that have a limited effect on tissue damage, researchers suggested.

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Eating Protein Before Carbohydrates May Improve Glycemia

• Food order may have a significant impact on postprandial glucose and insulin levels, according to a new study.

• This pilot study included 11 patients who had metformin-treated type 2 DM and were obese. After a 12-hour overnight fast, they consumed an isocaloric meal with the same composition on 2 separate days, 1 week apart.

• The first day, the patients ate the carbohydrates first, followed by protein 15 minutes later. The second day, they switched the food order.

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Effect of Protein Before Carbohydrates Comparable to Drugs

• When protein was consumed first, mean post-meal glucose levels were decreased by 28.6% at 30 minutes, 36.7% at 60 minutes, and 16.8% at 120 minutes.

• Postprandial insulin levels at 60 minutes and at 120 minutes also were significantly lower.

• The magnitude of the effect was comparable to that observed with drugs that preferentially target postprandial glucose.

• Rather than focus on “how much to eat” and “what not to eat,” patients might optimally time carbohydrate ingestion during a meal for greater success in improving glycemia, the researchers suggested.

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Potential Treatment for Diabetes-related Heart Damage

• Glucose toxicity in the heart is one of the gravest complications of DM, and the mechanisms of toxicity are poorly understood.

• Now Johns Hopkins researchers have found that a sugar molecule, O-GIcNAc, and the transferase enzyme that cleaves it could be responsible.

• In a rat model, they found that the sugar and enzyme move into the control center of muscle contraction and disrupt contractions.

• Preventing this displacement of the sugar and enzyme may represent a possible new strategy for treating diabetic cardiomyopathy.

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Genetic Predisposition to Obesity Linked With Higher Diabetes Risk

• Abdominal obesity is a major risk factor for type 2 DM.

• Researchers set out to examine the association between a genetic predisposition to central obesity, assessed by the waist-to-hip ratio genetic score, and the risk of type 2 DM.

• The study included 5643 participants of European ancestry (2591 who had type 2 DM and 3052 who did not) from the Nurses’ Health Study (women) and the Health Professionals Follow-up Study (men).

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Obesity Score Related to Higher Diabetes Risk

• The central obesity genetic score was linearly related to a higher risk of type 2 DM.

• Results were similar in women and men.

• In combined results, each point of the central obesity genetic score was associated with an odds ratio of 1.04 for type 2 DM developing.

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Central Obesity Mediates Higher Diabetes Risk

• After multivariate adjustment, the odds ratio was 1.24 when extreme quartiles of the genetic score were compared.

• The data indicate that genetic predisposition to central obesity is associated with a higher risk of type 2 DM.

• The researchers concluded that this association is mediated by central obesity.

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Take-home Messages:

• Targeting senescent cells may offer a therapeutic opportunity in the prevention and treatment of type 2 DM and its complications.

• Eating foods rich in protein before carbohydrates may help lower postprandial glucose and insulin levels in patients with type 2 DM.

• New research maps out the molecular chain of events inside cells that is responsible for the heart muscle damage seen in DM.

• A genetic predisposition to central obesity is linked to a higher risk of type 2 DM.