Gestational Diabetes Mellitus in Early Pregnancy: Evidence for Poor Pregnancy Outcomes Despite Treatment

Recent guidelines recommend testing at <24 weeks of gestation for maternal dysglycemia in "high-risk" women. Evidence to support the early identification and treatment of gestational diabetes mellitus (GDM) is, however, limited. We examined the prevalence, clinical characteristics, and pregnancy outcomes of high-risk women with GDM diagnosed at <24 weeks of gestation (early GDM) and those with pre-existing diabetes compared with GDM diagnosed at ≥24 weeks of gestation, in a large treated multiethnic cohort.

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this.

Effects of Age, Diabetes, and Vascular Disease on Growth Differentiation Factor 11: First-in-Human Study

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β superfamily, has been recently described as a soluble rejuvenation factor for the heart, muscle, and brain. In fact, GDF11 declines in aged mice, while its replenishment improves vascular, brain, muscle, and cardiac function (1–3). As type 2 diabetes (T2D) increases with age and is characterized by accelerated aging (4), we cross-sectionally explored the effects of age, diabetes, and vascular disease on plasma GDF11 concentrations. The study was approved by the local ethics committee and conducted in accordance with the principles of the Declaration of Helsinki. Plasma GDF11 concentrations were measured by ELISA (MBS2502734, MyBioSource) in a previously described cohort of T2D patients and age- and sex-matched control subjects without diabetes (5). As the distribution of GDF11 concentrations was skewed, it was log-transformed before statistical analyses. On average, plasma GDF11 concentrations were higher in T2D patients than …

Response to Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care 2015;38:308–315

We thank Dr. Takahara (1) for the comment on our recent article exploring the impact of HbA1c, followed from diabetes onset, on the development of severe microvascular complications (2). As suggested, we have validated our results with Cox hazards analysis with severe microvascular events, i.e., laser-treated proliferative retinopathy and macroalbuminuria …

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c

OBJECTIVE Glucokinase monogenic diabetes (GCK–maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. RESEARCH DESIGN AND METHODS Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). RESULTS Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5–1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. CONCLUSIONS The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored.

Comment on Krul-Poel et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care 2015;38:1420–1426

Efficacy and Safety of Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes

OBJECTIVE This study assessed the efficacy and safety of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, as add-on to insulin in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This 18-week, double-blind, phase 2 study randomized 351 patients (HbA1c 7.0–9.0% [53–75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion to canagliflozin 100 or 300 mg or placebo. The primary end point was the proportion of patients achieving at week 18 both HbA1c reduction from baseline of ≥0.4% (≥4.4 mmol/mol) and no increase in body weight. Other end points included changes in HbA1c, body weight, and insulin dose, as well as hypoglycemia incidence. Safety was assessed by adverse event (AE) reports. RESULTS More patients had both HbA1c reduction ≥0.4% and no increase in body weight with canagliflozin 100 and 300 mg versus placebo at week 18 (36.9%, 41.4%, 14.5%, respectively; P &lt; 0.001). Both canagliflozin doses provided reductions in HbA1c, body weight, and insulin dose versus placebo over 18 weeks. The incidence of hypoglycemia was similar across groups; severe hypoglycemia rates were low (1.7–6.8%). Overall incidence of AEs was 55.6%, 67.5%, and 54.7% with canagliflozin 100 and 300 mg and placebo; discontinuation rates were low (0.9–1.3%). Increased incidence of ketone-related AEs (5.1%, 9.4%, 0%), including the specific AE of diabetic ketoacidosis (DKA) (4.3%, 6.0%, 0%), was seen with canagliflozin 100 and 300 mg versus placebo. CONCLUSIONS Canagliflozin provided reductions in HbA1c, body weight, and insulin dose with no increase in hypoglycemia, but increased rates of ketone-related AEs, including DKA, in adults with type 1 diabetes inadequately controlled with insulin.

Erratum. Small Fiber Neuropathy in Patients With Latent Autoimmune Diabetes in Adults. Diabetes Care 2015;38:e102–e103

Clinical Considerations for Insulin Pharmacotherapy in Ambulatory Care, Part Two: Review of Primary Literature and an Evidence-Based Approach for Treatment

IN BRIEF This article reinforces the dosing guidance from the package inserts of available insulin products and supplemental information provided by the manufacturers of insulin products. It reviews and evaluates pertinent primary literature detailing algorithms for the initiation and titration of insulin therapy that have helped to shape current clinical practice guidelines. The article discusses the clinical applicability of the evidence on insulin pharmacotherapy and offers recommendations for initiation and titration of various insulin products for insulin-requiring people with type 2 diabetes in the ambulatory care setting.

A Red-violaceous Papular Lesion in a Young Girl: A Quiz