Kerstin Berntorp

Glucose tolerance and smoking: A population study of oral and intravenous glucose tolerance tests in middle-aged men

SummaryThe oral and intravenous glucose tolerance tests have been compared in middle-aged, normal-weight male non-smokers, ex-smokers and smokers who participated in a general health screening programme in Malmö, Sweden. Subjects with diabetes, previous gastric resection and/or present medication with diuretic agents were excluded. No difference was found when comparing fasting glucose in non-smokers, ex-smokers and smokers. In the oral glucose tolerance test, plasma glucose at 40 and 60 min increased stepwise from nonsmokers (8.7 and 7.4 mmol/l) to ex-smokers (8.9 and 7.5 mmol/1), smokers (9.2 and 7.9 mmol/1) and heavy smokers (9.7 and 8.2 mmol/1). Blood glucose levels at 120 min were inversely arranged. Plasma insulin at 120 min was lower in heavy smokers (16.2 mU/1) than in non-smokers (24.8 mU/1). The mean intravenous glucose tolerance test k-value was lower in smokers than in non-smokers. K-values below 1.0 were twice as common in smokers (30%) as in non-smokers. It is concluded that smoking has a clinically significant influence on both the oral and intravenous glucose tolerance tests.

A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

Aims/hypothesisGenetic and epidemiological studies suggest an association between gestational diabetes mellitus and type 2 diabetes. Both are polygenic multifactorial disorders characterised by beta cell dysfunction and insulin resistance. Our aim was to investigate whether common genetic variants that have previously been associated with type 2 diabetes or related phenotypes would also confer risk for gestational diabetes mellitus.Materials and methodsIn 1,881 unrelated pregnant Scandinavian women (649 women with gestational diabetes mellitus, 1,232 non-diabetic control subjects) we genotyped the transcription factor 7-like 2 (TCF7L2 rs7903146), adiponectin (ADIPOQ +276G > T), peroxisome-proliferator activated receptor, gamma 2 (PPARG Pro12Ala), PPARG-coactivator, 1 alpha (PPARGC1A Gly482Ser), forkhead box C2 (FOXC2 −512C > T) and β3-adrenergic receptor (ADRB3 Trp64Arg) polymorphisms using TaqMan allelic discrimination assay or RFLP.ResultsThe CC, CT and TT genotype frequencies of the TCF7L2 rs7903146 variant differed significantly between women with gestational diabetes mellitus and control women (46.3, 43.6 and 10.1% vs 58.5, 35.3 and 6.2%, p = 3.7 × 10−6, corrected p value [Pc] for multiple testing Pc = 2.2 × 10−5). The T-allele was associated with an increased risk of gestational diabetes mellitus (odds ratio 1.49 [95% CI 1.28–1.75], p = 4.9 × 10−7 [Pc = 2.8 × 10−6]). Compared with wild-type CC-genotype carriers, heterozygous (CT-genotype) and homozygous (TT-genotype) carriers had a 1.6-fold (95% CI 1.26–1.93, p = 3.7 × 10−5 [Pc = 0.0002]) and a 2.1-fold (95% CI 1.41–2.99, p = 0.0001 [Pc = 0.0008]) increased risk of gestational diabetes mellitus, respectively. The other polymorphisms studied were not significantly associated with gestational diabetes mellitus (ADIPOQ +276G > T: 1.17 [1.01–1.36], p = 0.039 [Pc = 0.23]; PPARG Pro12Ala: 1.06 [0.87–1.29], p = 0.53; PPARGC1A Gly482Ser: 0.96 [0.83–1.10], p = 0.54; FOXC2 −512C > T: 1.01 [0.87–1.16], p = 0.94; and ADRB3 Trp64Arg: 1.22 [0.95–1.56], p = 0.12).Conclusions/interpretationThe TCF7L2 rs7903146 variant is associated with an increased risk of gestational diabetes mellitus in Scandinavian women.

Pregnancy rate and outcome in Swedish women with Turner syndrome

Pregnancies occurred in 57 (12%) of 482 Swedish women with Turner syndrome with a liveborn rate of 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40%, mainly in women with 45,X/46,XX mosaicism, and oocyte donation in 53% where miscarriages were less frequent, odds ratio = 0.43 (95% confidence interval 0.17-1.04).

Intensive glucose therapy and clinical implications of recent data: a consensus statement from the Global Task Force on Glycaemic Control

Background:  There is compelling evidence showing that achieving good glycaemic control reduces the risk of microvascular complications in people with type 1 and type 2 diabetes. Likewise, there is clear evidence to show that achieving good glycaemic control reduces the risk of macrovascular complications in type 1 diabetes. The UKPDS 10‐year follow up suggests that good glycaemic control also reduces the risk of macrovascular complications in type 2 diabetes. Despite this, recent results from ACCORD, ADVANCE and VADT present conflicting results and data from the ACCORD trial appear to suggest that very low HbA1c targets (<6.0%) may, in fact, be dangerous in certain patient populations.

Common variants in MODY genes increase the risk of gestational diabetes mellitus.

Aims/hypothesisImpaired beta cell function is the hallmark of gestational diabetes mellitus (GDM) and MODY. In addition, women with MODY gene mutations often present with GDM, but it is not known whether common variants in MODY genes contribute to GDM.Subjects and methodsWe genotyped five common variants in the glucokinase (GCK, commonly known as MODY2), hepatocyte nuclear factor 1-α (HNF1A, commonly known as MODY3) and 4-α (HNF4A commonly known as MODY1) genes in 1,880 Scandinavian women (648 women with GDM and 1,232 pregnant non-diabetic control women).ResultsThe A allele of the GCK −30G→A polymorphism was more common in GDM women than in control subjects (odds ratio [OR] 1.28 [95% CI 1.06−1.53], p=0.008, corrected p value, p=0.035). Under a recessive model [AA vs GA+GG], the OR increased further to 2.12 (95% CI 1.21−3.72, p=0.009). The frequency of the L allele of the HNF1A I27L polymorphism was slightly higher in GDM than in controls (1.16 [95% CI 1.001−1.34], p=0.048, corrected p value, p=0.17). However, the OR increased under a dominant model (LL+IL vs II; 1.31 [95% CI 1.08−1.60], p=0.007). The rs2144908, rs2425637 and rs1885088 variants, which are located downstream of the primary beta cell promoter (P2) of HNF4A, were not associated with GDM.Conclusions/interpretationThe −30G→A polymorphism of the beta-cell-specific promoter of GCK and the I27L polymorphism of HNF1A seem to increase the risk of GDM in Scandinavian women.

Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus

Aims/hypothesisGestational 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 methodsWe 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).ResultsThe 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/interpretationThe E23K polymorphism of KCNJ11 seems to predispose to GDM in Scandinavian women.

Effects of insulin vs. glibenclamide in recently diagnosed patients with type 2 diabetes: a 4-year follow-up.

Aim:  To compare effects of early insulin vs. glibenclamide treatment on beta‐cell function, metabolic control and quality of life (QL) in recently diagnosed patients with type 2 diabetes.

A simplified oral glucose tolerance test in pregnancy : compliance and results

Background. To describe a reliable method for a general oral glucose tolerance test (OGTT) during pregnancy, to evaluate adherence to the method, and to compare the frequency of reported gestational diabetes mellitus (GDM) and perinatal outcome in affected pregnancies in Skåne, using direct diagnostic OGTT, with those from a comparable area, Halmstad‐Ljungby‐Växjö (HLV), using random glucose measurements (RGM) to identify women for the OGTT. Methods. The OGTT program and quality assurance in Skåne is described. Antenatal records on deliveries in May 2003 were scrutinised to ascertain if OGTT had been performed. Frequencies of GDM, prematurity and large for gestational age (LGA) infants were estimated using a population‐based perinatal database (PRS). Results. OGTT was performed in 93% of pregnant women in Skåne. In 2000–2003 GDM frequency in Skåne was twice as high as in HLV (1.9 versus 1%), while the frequency of LGA and prematurity among infants of mothers who were diagnosed with GDM were similar. Conclusions. Decentralised general OGTT is a reliable and effective method to diagnose GDM. OGTT is twice as sensitive as RGM, and the severity of GDM in the cases identified with OGTT did not differ from the severity of those identified with RGM.

Liposuction in Dercum's disease: impact on haemostatic factors associated with cardiovascular disease and insulin sensitivity.

Berntorp E, Berntorp K, Brorson H, Frick K (University of Lund, Malmö, Sweden). Liposuction in Dercums disease: impact on haemostatic factors associated with cardiovascular disease and insulin sensitivity. J Intern Med 1998; 243: 197–201.

Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus

AIMS To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). METHODS 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. RESULTS After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p=0.00016 after adjustment for age and ethnicity). CONCLUSIONS 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.