Recent updates in diabetes : Dr Srikant Sharma

On eve of World Diabetes day, Dr Srikant Sharma has authored an Update on Diabetes.

Eating nuts instead of carbs could improve blood sugar in Type 2 diabetes:

Nuts added to a meal will reduce the glycaemic load of the meal. The presence of lipids together with antinutrients, such as phytates and antioxidant phenolics, may delay gastric emptying and the rate o small intestinal absorption, resulting in a flatter postprandial glycaemic response. Diabetologia2018:61(8)].

Saliva could provide a painless diabetes test for children:

The issue of children’s compliance in monitoring their serum glucose has shifted researchers’ focus toward saliva.
Analysis demonstrated alterations in the salivary proteomic values of various serum originating proteins - related to increased levels of HbA1c. Differentially expressed salivary proteins are related to acute phase response, endothelial dysfunction, inflammatory and coagulation processes in T1DM. (Front.physiol. 9:444.)

Antibiotics early in childhood could increase the risk of Type 1 diabetes:

Antibiotic administration in early life alters intestinal microbial populations and their products which differentially interact with ileal epithelial cells causing the change in gene expression and cell maturation. This also alters adaptive immunity and host gene expression which may trigger and accelerate T1DM.(eLife 2018;7:e37816.).

Diabetes identified as higher risk factor for cancer in women than men:

Systematic review and meta-analysis of 121 cohorts, has shown: Women with diabetes had ~6% greater risk of cancer compared with men having diabetes. Diabetes also conferred a significantly greater risk in women than men for oral, stomach and kidney cancer, and for leukaemia. (Diabetologia2018)

Canagliflozin (Invokana) slows kidney disease progression:

Phase 3 CREDENCE Renal Outcomes Trial of canagliflozin has shown: Canagliflozin has the potential for slowing the progression of chronic kidney disease in patients with type 2 diabetes.

Full-fat dairy improves heart health in a new 22-year study:

Long-term exposure to circulating biomarkers of dairy fat was not significantly associated with total mortality or incident CVD among older adults.
In fact High circulating heptadecanoic acid ( one of the biomarkers of dairy fat) was inversely associated with CVD (i.e improves heart health) and stroke mortality. (Am J Clin Nutr 2018;108:1-9).

Partners of people with type 2 diabetes are more likely to improve their health:

The study showed that the partners of persons with diabetes make positive changes in health care seeking and health behaviours compared with partners of persons without diabetes. Diabetes diagnosis may affect household members’ perceptions of their own health risks, which could
trigger behavioural change. (AnnFamMed 2018;16:290-295).

Young overweight boys who lose weight by puberty could halve type 2 diabetes risk:

Weight reduction reduced adverse effects (i.e risk of diabetes) if the subject was: OVERWEIGHT at 7 years and became normal weight before puberty as well as maintained this normal status in early childhood. OVERWEIGHT status at 13 yrs and the entire span of early childhood was associated with a high risk of T2DM irrespective of weight status at 7yrs. (Bjerregaard et.al. Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes. (N Engl J Med 2018;378:1302-12).

Blood pressure drug verapamil restores beta cell function in new-onset type 1 diabetes

clinical trial: once-daily oral verapamil added to a standard insulin regimen may provide a safe and effective novel approach to promote and preserve beta cell function. As per randomized double-blind placebo-controlled phase 2, delay beta cell loss and disease progression for at least 1 year and reduce insulin requirements and hypoglycemic episodes in adults with recent-onset type1diabetes(T1D). This was randomized double-blind placebo-controlled phase 2 clinical trial to assess the efficacy and safety of oral verapamil added for 12 months to a standard insulin regimen in adult subjects with recent-onset T1D.
End-points:- Primary: Mixed-meal-stimulated C-peptide area under the curve ( a measure of endogenous beta cell function) at 3 and 12 months
Secondary endpoints: lower increase in insulin requirements, fewer hypoglycemic events and on-target glycemic control Conclusion: once-daily oral verapamil added to a standard insulin regimen may provide a safe and effective the novel approach to promote and preserve beta cell function, delay beta cell loss and disease progression for at least 1 year and reduce insulin requirements and hypoglycemic episodes in adults with recent-onset T1D.Proposed Mechanism: verapamil- by decreasing the expression of the thioredoxin-interacting protein, promotes the survival of insulin-producing beta cells. ( Nature Medicine .https://doi.org/10.1038/ s41591-018-0089-4.)

Improving air quality could reduce type 2 diabetes diagnosis:

Based on the findings of the longitudinal cohort study for a median period of 8.5 yrs involving 1·7 million US veterans. The study shows that substantial risk for diabetes exists at PM 2·5 concentrations well below those outlined in the air quality standards of WHO and national and international regulatory agencies. (WWW.thelancet.com/planetary- health vol 2 July 2018)

US study reports a newer generation of insulin shows no difference to older versions:

Based on a retrospective cohort study comparing basal insulins vs NPH, Outcomes: Initiation of basal insulin analogues compared with NPH insulin was not associated with a lower rate of ED visits or hospital admissions related to hypoglycemia. No significant Difference between both the groups in terms of glycaemic control. Limitations of the study It’s an observational study, there might be many confounding factors between both the group. The study only considered hospital admission due to hypoglycemia thus nocturnal/ self-reported hypoglycemia were not accounted for. Based on a retrospective cohort study comparing basal insulins vs NPH Endpoints:- Primary: Time to an emergency department (ED) visit or hospital admission for hypoglycemia. (JAMA July 3, 2018 volume 320, number1)

BCG vaccine found to strongly improve HbA1c in type 1 diabetes:

Based on a randomized 8-year long prospective examination of type 1 diabetic subjects who received two doses (4 wks apart) of the BCG vaccine
Outcomes: After year 3, BCG lowered haemoglobin A1c to near normal levels for the next 5 years. BCG causes a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis (a state of high glucose utilization). BCG induces genetic reprogramming to increase glucose tolerance.(npj vaccines 2018, 3:23)

Quitting smoking and controlling diabetes may reduce dementia risk in old age

Outcome: diabetes mellitus and smoking were associated with an increased risk of hippocampal calcifications. Based on a retrospective study which compared the association between vascular risk factors (hypertension, diabetes mellitus, hyperlipidemia & smoking) and hippocampal calcifications as well as cognitive function. (Radiology journal 2018)

Next Generation Basal insulin with a different PK/PD:

The new glargine-300 formulation: Has a flatter and more extended time-action profile than the original glargine-100. These characteristics may translate into more stable and sustained glycemic control over a 24 h dosing interval. (Journal of diabetes research volume 2018)

A smart patch could make insulin delivery less painful for people with diabetes:

A glucose-responsive “closed-loop” insulin delivery system using a painless microneedle-array patch (“smart insulin patch”) containing glucose responsive vesicles (GRVs). GRVs are self-assembled from hypoxia-sensitive hyaluronic acid (HS-HA).

The local hypoxic microenvironment caused by the enzymatic oxidation of glucose in the hyperglycemic state promotes the reduction of HS-HA, which rapidly triggers the dissociation of vesicles and subsequent release of insulin

Open-flame and/or high-temperature cooking (grilling/barbecuing, broiling, or roasting) of meat/ chicken increases diabetes risk

Based on a prospective study: Independent of consumption amount, open-flame and/or high-temperature cooking for both red meat and chicken is associated with an increased T2DM risk among adults who consume animal flesh regularly. (Diabetes Care 2018;41:1049-1060)

Legacy effect of intensive glucose control may not last beyond a certain period:

Based on Veterans Administration Diabetes Trial (VADT):
Shows that 5.6 years or more versus less glucose lowering -reduces the 10-year risk of cardiovascular events, but there's no effect after 15 years (17% Reduction in Cardiovascular Events at 10 Years, None at 15 Years). No strong evidence of & 'metabolic memory' or a 'legacy effect’ till now.
Gliptins might be associated with IBD: Based on a cohort study: Use of Dipeptidyl Peptidase-4 Inhibitors is associated with an overall increase in the risk of inflammatory bowel disease in patients with T2DM. BUT absolute risk is low. There should be a caution while prescribing DPP4i in patients with high risk of IBD.
Cohort study Outcome: the use of dipeptidyl peptidase-4 inhibitors is associated with an overall 75% increase in the risk of inflammatory bowel disease in patients with type 2 diabetes (BMJ 2018;360: K872)

Breastfeeding reduces the risk of T2DM Outcome: Among young white and black women in this observational 30-year study, increasing lactation duration was associated with a strong, graded 25% to 47% relative reduction in the incidence of diabetes. This US community-based CARDIA study provides a biochemical basis for strong, graded inverse associations between lactation duration and incidence of diabetes in women of childbearing age.

Dr Srikant Sharma is Senior Consultant Physician, Moolchand Hospital, New Delhi.