Aims/hypothesis We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes. Methods We monitored 174 women with gestational diabetes by performing oral glucose tolerance tests during pregnancy as well as 1, 2 and 5 years postpartum. Women who developed impaired fasting glucose, impaired glucose tolerance or diabetes were compared with women who remained normoglycaemic at 5 years. Insulinogenic index, disposition index and HOMA-beta cell index were used to assess beta cell function; insulin resistance was estimated by HOMA index of insulin resistance. Results At 5 years postpartum, 30% of the women had developed diabetes and 51% some form of abnormal glucose tolerance. Women who developed diabetes had higher fasting glucose and HbA 1c during pregnancy than those who remained normoglycaemic. They also had lower HOMAbeta cell index, insulinogenic index and disposition index than the normoglycaemic women. HbA 1c and fasting glucose during pregnancy as well as the number of previous pregnancies and family history of diabetes were independent predictors of postpartum diabetes. HbA 1c ≥4.7% (Swedish Mono S) or ≥5.7% (National Glycohemoglobin Standardization Program) and fasting blood glucose ≥5.2 mmol/l were associated with a four-to sixfold increased risk.Conclusions/interpretation Among women with gestational diabetes mellitus, those at risk of future diabetes can be identified by HbA 1c and fasting glucose values in the upper normal range during pregnancy. A family history of diabetes and previous pregnancies further increase this risk.

Study queStion

To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes. RESEARCH DESIGN AND METHODSAfter a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years) to double-blind mealtime faster aspart (n = 260), mealtime IAsp (n = 258), or open-label postmeal faster aspart (n = 259). The primary end point was change from baseline in glycated hemoglobin (HbA 1c ) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect. RESULTSAt week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA 1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference 20.17% [95% CI 20.30; 20.03], 21.82 mmol/mol [23.28; 20.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose-confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp. CONCLUSIONSIn children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA 1c control compared with IAsp.

Aims/hypothesis: Gestational diabetes mellitus (GDM) and type 2 diabetes share a common pathophysiological background, including beta cell dysfunction and insulin resistance. In addition, women with GDM are at increased risk of developing type 2 diabetes later in life. Our aim was to investigate whether, like type 2 diabetes, GDM has a genetic predisposition by studying five common polymorphisms in four candidate genes that have previously been associated with type 2 diabetes. Materials and methods: We studied 1,777 unrelated Scandinavian women (588 with GDM and 1,189 pregnant non-diabetic controls) for polymorphisms in the genes encoding potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11 E23K), insulin receptor substrate 1 (IRS1 G972R), uncoupling protein 2 (UCP2 −866G→A) and calpain 10 (CAPN10 SNP43 and SNP44). Results: The EE, EK and KK genotype frequencies of the KCNJ11 E23K polymorphism differed significantly between GDM and control women (31.5, 52.7 and 15.8% vs 37.3, 48.8 and 13.9%, respectively; p=0.050). In addition, the frequency of the K allele was increased in women with GDM (odds ratio [OR]=1.17, 95% CI 1.02−1.35; p=0.027), and this effect was greater under a dominant model (KK/EK vs EE) (OR=1.3, 95% CI 1.05−1.60; p=0.016). Analysis of the IRS1 G972R polymorphism showed that RR homozygosity was found exclusively in women with GDM (91.0, 8.3 and 0.7% vs 90.7,9.3 and 0.0% for GG, GR and RR genotypes, respectively; p=0.014). The genotype and allele frequencies of the other polymorphisms studied were not statistically different between the GDM and control women. Conclusions/interpretation: The E23K polymorphism of KCNJ11 seems to predispose to GDM in Scandinavian women.

OBJECTIVE -To investigate whether genetic susceptibility to type 1 diabetes or maturityonset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS -We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum.RESULTS -There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n ϭ 82) or healthy control subjects (n ϭ 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1␣ gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum.CONCLUSIONS -MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes. Diabetes Care 25:68 -71, 2002

IntroductionNon-diabetic ketoacidosis is a rare condition which can be caused by starvation. Lack of glucose can force the body into ketogenesis causing a metabolic acidosis. As previously reported in the literature, ketoacidosis might, on rare occasions, be caused by a diet with low carbohydrate content. However, to the best of our knowledge this is the first reported case in the literature of ketoacidosis, in a non-diabetic patient, associated with a combination of low carbohydrate, high fat diet and lactation.Case presentationA healthy non-diabetic, 32-year old white woman started a low carbohydrate, high fat diet when she was breastfeeding her son of 10 months of age. After 10 days she was admitted to our hospital with nausea and vomiting and a serum pH of 7.20 and base excess of −19. Clinical signs and blood samples were compatible with ketoacidosis. She was given fluids intravenously and insulin. No anamnestic or clinical signs of diabetes were found. She recovered quickly and was discharged 3 days later.ConclusionsKetogenic diets like low carbohydrate, high fat may induce ketoacidosis. Lactation might further aggravate the condition and can perhaps even be the trigger into ketoacidosis. Health services should be aware of the risks associated with ketogenic diets, and be able to recognize this serious condition when it is presented.

The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.

IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.