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We explored glucometabolic and renal function after engraftment in all 159 consecutive patients with type 1 diabetes who received pancreas transplantation alone (PTA, n  = 80) or simultaneous pancreas and kidney transplantation (SPK, n  = 79) in Norway from 2012 until 2017. We report fasting levels of plasma glucose (FPG), C-peptide, eGFR and the homeostasis model assessment of insulin sensitivity (HOMA2(%S)) and beta-cell function (HOMA2(%B)) measured one to three times weekly during the first 8 and at 52 weeks after transplantation. One year after engraftment, in the PTA and SPK groups 52 and 64 were normoglycaemic without exogenous insulin, and two and zero patients were dead. Data at the 52-week visit were missing for 5 and 6 patients in the respective groups. During the first 8 weeks, FPG was lower, C-peptide and HOMA2(%S) were higher and eGFR was lower in the SPK group as compared with the PTA group (all p  < .05). 30 out of 157 living patients needed insulin treatment 52 weeks after transplantation, 9/79 in the SPK group and 21/78 in the PTA group ( p  = .02). In conclusion, patients who underwent SPK showed lower insulin sensitivity, but higher insulin secretory capacity and lower mean blood glucose levels the first 8 weeks after transplantation. Also, a higher proportion of patients in the SPK group were insulin-free after 1 year, compared with the PTA group.

Impaired insulin secretion and action are important for development of type 2 diabetes (T2D) and metabolic syndrome (MetS). Despite recognized heterogeneity of these glucometabolic disorders, few data are available of biological variation in insulin secretion and action among individuals with T2D and MetS. The aim of this study was to explore the inter-individual variations using gold standard methods in a cross-sectional study of two independent cohorts of phenotypically well-characterized subjects. Cohort I included 486 subjects with MetS, and cohort II 62 subjects with established T2D. First phase insulin secretion was defined as the incremental area under the curve 0-8 min (iAUC 0-8 min ) during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured as the insulin sensitivity index (S I ) modelled from IVGTT in cohort I, and in II as total glucose disposal (TGD) estimated from a euglycaemic-hyperinsulinaemic clamp. Variation is given as total range and, fold-variation between 5%- and 95%-percentile. The iAUC 0-8 min ranged from -60 to 3397 mUL -1 min -1 among subjects with MetS and from -263 to 1194 mUL -1 min -1 in subjects with T2D, representing a more than 10-fold variation. Insulin sensitivity ranged from S I 0.19 to 15.29 (mU/L) -1 min -1 among subjects with MetS and TGD 12.9-101.6 μmolkgFFM -1 min -1 in subjects with T2D, representing a 6.8 and 5.5-fold variation, respectively. The other components of MetS; BMI, waist-hip ratio, HDL-cholesterol, triglycerides and blood pressure (BP), showed a 1.4-4.7-fold variation. In conclusion, our data demonstrated extensive inter-individual variations in insulin secretion and sensitivity. These variations may be essential to take into account when planning clinical research and treatment in subjects with T2D and MetS.

Background: Modern metabolomic profiling has not yet been applied to human breastfeeding research. A common reason for breastfeeding cessation is perceived insufficient milk production. We investigated broad biochemical profiles in maternal urine collected during and after pregnancy to identify biomarkers related to reduced reported breastfeeding., Methods: Fasting urine was collected at three consultations (visit V1: gestational week 8-20; V2: week 28 ± 2; V3: 10-16 weeks postpartum) in the STORK Groruddalen program, a prospective, multiethnic cohort study of gestational diabetes involving healthy, pregnant women in Oslo, Norway, and analyzed using NMR spectroscopy. Breastfeeding at V3 was recorded in three categories: Exclusively breastfeeding (n = 326), partially breastfeeding (n = 156) and formula feeding (n = 67)., Results: Five metabolites were relevant to breastfeeding. Lactose was detected at V1 and increased to 0.1 mM/mM creatinine at V2. Postpartum excretion at V3 was significantly higher in exclusively breastfeeding women than partially or non-breastfeeding (median = 0.29, 0.23 and 0.04 mM/mM creatine, respectively; ANOVA p-value = 2e-70). Glycine excretion at V3 (0.12, 0.10 and 0.06, respectively; p = 2e-5) and at V2 were associated with breastfeeding (0.34, 0.33 and 0.26, respectively; p = 4e-5). Creatine and two unidentified substances also correlated with breastfeeding. NMR metabolomics found no other metabolites differing between categories during pregnancy (V1, V2), and did not predict individual breastfeeding postpartum (V3)., Conclusion: Decreased glycine excretion at V2 may indicate difficulties meeting the metabolic demands of the growing fetus, but urine profiles contained otherwise little indication of early adaptations during pregnancy towards reduced biological potential to breastfeed.

Unlabelled: We studied the impact of genetic and traditional risk factors for type 2 diabetes in a large, population-based study from Nord-Trøndelag county in Norway (HUNT), in both cross-sectional and prospective design., Material and Methods: 65,905 individuals participated in the HUNT study. We studied a randomly selected group of 869 individuals with self-reported diabetes or non-fasting serum glucose >or=11.1 mmol/L and 2,080 non-diabetic control subjects with non-fasting serum glucose <5.5 mmol/L. Four candidate polymorphisms in the three genes TCF7L2 (rs12255372 and rs7903146), PPARG (rs1801282), KCNJ11 (rs5219) and traditional risk factors were studied., Results: Risk alleles of the TCF7L2 gene showed increased risk of diabetes even when controlled for traditional diabetes risk factors (diabetes in family, waist circumference, physical activity, BMI, SBP and total and HDL-cholesterol) in both a cross-sectional and prospective setting (cross-sectional: rs12255372 OR 1.61 (1.31-1.99), rs7903146 OR 1.48 (1.20-1.83) and prospective: rs12255372 OR 1.59 (1.22-2.07), rs7903146 OR 1.47 (1.11-1.93)). The risk alleles of TCF7L2 indicated impaired beta-cell function in patients and control subjects. The population attributable risks for diabetes with TCF7L2 risk alleles were 15 % and with diabetes in a first-degree relative 31 %., Conclusion: The risk alleles of the TCF7L2 gene (rs12255372 and rs7903146) were strongly associated with type 2 diabetes, even after controlling for traditional risk factors in both a cross-sectional and prospective setting. These risk alleles were associated with indices of reduced beta-cell function.

Objective: Coronary artery disease (CAD) is prevalent in patients with type 2 diabetes mellitus (T2DM) and because it is often asymptomatic and extensive in comparison with CAD in subjects without diabetes, it represents a diagnostic challenge. The objective of the study was to investigate the prevalence of CAD in asymptomatic T2DM patients utilizing angiography and to investigate its association with cardiovascular (CV) risk factors, the metabolic syndrome and markers of inflammation., Material and Methods: Eighty-two patients with T2DM without symptoms of CAD, and with >or=1 CV risk factor (hypertension, dyslipidaemia, premature familial CAD, smoking or microalbuminuria) underwent a diagnostic stress test and coronary angiography irrespective of stress test results. Stenosis detected in the main coronary arteries >or=50% of lumen diameter was categorized as one-, two- or three-vessel disease. Inflammatory markers were analysed in fasting samples., Results: Fifteen men and two women had significant CAD (21%) (1-vessel disease, n=10; 2- or 3-vessel disease, n=7). Patients with 2- or 3-vessel disease were significantly older and had a longer duration of diabetes, but the prevalence of other traditional CV risk factors or the metabolic syndrome was similar among those with 1-vessel and those with 2- or 3-vessel disease. Sensitivity for CAD of the stress test was low (0.35). The mean level of the pro-inflammatory marker interleukin-6 was elevated in patients with 2- to 3-vessel CAD as compared to patients with no or 1-vessel CAD (p<0.05)., Conclusions: Significant CAD was found in 21% of asymptomatic patients with T2DM with >or=1 CV risk factor. Inflammatory markers may be helpful in identifying patients that are likely to have significant CAD, but larger studies are warranted.

Obesity and related disorders have become a major health problem. Understanding the interaction between genetic and environmental factors influencing the susceptibility to develop obesity is important when pinpointing people at risk. In a longitudinal study of 256 non-obese adolescents, the influence of the insulin gene (INS) variable number of tandem repeats (VNTR) on anthropometric measures and fat mass was investigated. The adolescents were examined at the age of 12.4 (2.3) (mean, SD) and 16.2 (2.3) years, and at follow-up with dual x-ray absorptiometry (DXA) for measurement of body composition. INS VNTR classes I and III alleles were investigated using the -23T/A single nucleotide polymorphism as a surrogate marker. There was a non-significant trend towards increased body mass index (BMI) and fat mass with the class III allele in girls. Homozygotes for the INS VNTR class III allele had a greater increase in BMI compared with those that were homozygous or heterozygous for the class I allele (3.8 (1.6) versus 2.4 (1.9) kg/m2, p = 0.03), and they had higher fat mass (36.4 (3.9) versus 31.3 (6.8)%, p = 0.02) at follow-up. Our finding that homozygosity of the INS VNTR class III allele seems to predispose to increased weight gain and fat mass raises the possibility that this genotype may be one of the important factors in the gene-environment interaction that eventually results in overweight and insulin resistance.

In view of the contradictory results of earlier reports regarding bone mass in patients with non-insulin-dependent diabetes, we measured bone mass using dual X-ray absorptiometry and ultrasound measurements of the right calcaneus in 36 type 2 diabetic subjects, i.e. 21 men and 15 postmenopausal women aged 40-65 years, and compared their bone mass to a sex- and age-matched control group. We also measured several metabolic parameters in the diabetic population and studied the relationship between these metabolic parameters and the bone parameters using correlation analysis. We found a tendency to higher bone mass in the diabetic subjects compared to the normal controls. In the Type 2 diabetic postmenopausal women, fat mass and lean body mass correlated positively with total body bone mineral density (BMD) (r = 0.53 and 0.68), and with total body bone mineral content (BMC) (r = 0.58 and 0.77). Insulin sensitivity (GDR/I) correlated negatively with total body BMC and BMD (r = -0.68 and -0.61). Serum insulin correlated positively with the same bone parameters. When controlling for fat mass or lean body mass using a multiple regression analysis, the correlation between insulin sensitivity and BMD became non-significant. This suggests that body mass is a more important determinant of BMD than hyperinsulinaemia or insulin resistance in diabetic women. Among the diabetic men there was a significant positive correlation between lean body mass and BMC (r = 0.66), between serum oestrone and BMD (r = 0.49) and between serum insulin and femoral neck BMD (r = 0.53).(ABSTRACT TRUNCATED AT 250 WORDS)

The introduction of two-site immunometric assays measuring intact parathyroid hormone (PTH) and radioimmunoassays measuring PTH-related peptide (PTH-RP) have simplified the evaluation of patients with hypercalcaemia. We present a 63-year-old man with recurrent hypercalcaemia after surgical treatment for primary hyperparathyroidism 3 years previously. PTH measured with a mid-region radioimmunoassay gave normal values, at the same level as during his primary hyperparathyroidism. Intact PTH was, however, clearly suppressed, and he had a highly elevated level of PTH-RP. This suggested that he had humoral hypercalcaemia of malignancy. The patient died after 2 months, and at autopsy an adenocarcinoma of the pancreas with no skeletal metastases was found.