Course of HbA1c in non-diabetic pregnancy related to birth weight

Obstetric

Whole body and hepatic insulin action in normal, starved, and diabetic rats

In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo dose-response relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]glucose infusion. Twelve-hour fasting (basal) HGP was 3.0 ± 0.2, 2.1 ± 0.2, and 5.4 ± 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from ±20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 ± 11 µU/ml) in S and unchanged (113 ± 21 µU/ml) in D compared with N rats (105 ± 10 µU/ml). Insulin responsiveness was unchanged (12.4 ± 0.8 mg/min) in S and decreased (8.5 ± 0.8 mg/min) in D compared with N rats (12.3 ± 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 ± 10 µU/ml) in S and decreased (157 ± 21 µU/ml) in D compared with N rats (71 ± 5 µU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (10-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se.

Long-term follow-up of organ-specific antibodies and related organ dysfunction in type 1 diabetes mellitus

OBJECTIVE Diabetes mellitus type 1 (DM1) is associated with other autoimmune disorders. To our knowledge, there are no longitudinal data considering the long-term clinical relevance of organ-specific antibodies (OS-Ab) in DM1 patients. We performed a long-term retrospective longitudinal study in order to investigate the presence and diagnostic accuracy (positive predictive value: PPV and negative predictive value: NPV) of OS-Ab in DM1 patients. RESEARCH DESIGN AND METHODS In a retrospective longitudinal study, the presence of OS-Ab and related organ function were analysed in 396 DM1 patients (184 F/212 M, age 44 ± 13 years, age at onset of DM1 21 ± 13 years), with a median follow-up time of 23 ± 10 years. RESULTS OS-Ab frequencies at baseline were: antibodies against thyroglobulin (Tg-Ab) 4.3%, antibodies against thyroid peroxidase (TPO-Ab) 8.1%, Tg- and/or TPO-Ab 10.4%, antibodies against parietal cells (PCA) 5.8% and antibodies against adrenal cortex (ACA) 0.5%. The occurrence of (sub)clinical hypothyroidism was higher in patients with Tg-Ab (47%) or TPO-Ab (42%) than in those without these antibodies (6.2 and 5.1%, respectively, p<0.001). PPV and NPV for Tg-Ab were 0.60 and 0.88, respectively, for TPO -Ab 0.54 and 0.91. Also in patients with PCA, organ dysfunction occurred more often (61%) than in patients without PCA (9.7%, p<0.001). PPV for PCA was 0.61 and NPV 0.90. NPV and PPV for ACA could not be calculated because of the low prevalence. Conclusion: Long-term follow-up of 396 DM1 patients shows that the presence of thyroid antibodies and/ or parietal cell antibodies is clearly associated with dysfunction of the corresponding organ.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Long-term follow-up of organ-specific antibodies and related organ dysfunction in type I diabetes mellitus

Diabetes mellitus: pathophysiological changes and therap

Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1

Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial pressure in hyperlipidaemic transgenic mice overexpressing apolipoprotein C1 (APOC1). Previous studies have shown that APOC1 transgenic mice develop hyperlipidaemia primarily because of an impaired hepatic uptake of very low density lipoprotein (VLDL). Methods. Basal and hyperinsulinaemic (6 mU ? kg-1 ? min-1), euglycaemic (7 mmol/l) clamps with 3-3H-glucose or 9,10-3H-palmitic acid infusions and in situ freeze clamped tissue collection were carried out. Results. The APOC1 mice showed increased basal plasma cholesterol, triglyceride, NEFA and decreased glucose concentrations compared with wild-type mice (7.0 ± 1.2 vs 1.6 ± 0.1, 9.1 ± 2.3 vs 0.6 ± 0.1, 1.9 ± 0.2 vs 0.9 ± 0.1 and 7.0 ± 1.0 vs 10.0 ± 1.1 mmol/l, respectively, p < 0.05). Basal whole body glucose clearance was increased twofold in APOC1 mice compared with wild-type mice (18 ± 2 vs 10 ± 1 ml ? kg-1 ? min-1, p < 0.05). Insulin-mediated whole body glucose uptake, glycolysis (generation of 3H2O) and glucose storage increased in APOC1 mice compared with wild-type mice (339 ± 28 vs 200 ± 11; 183 ± 39 vs 128 ± 17 and 156 ± 44 vs 72 ± 17 μmol ? kg-1 ? min-1, p < 0.05, respectively), corresponding with a twofold to three-fold increase in skeletal muscle glycogenesis and de novo lipogenesis from 3-3H-glucose in skeletal muscle and adipose tissue (p < 0.05). Basal whole body NEFA clearance was decreased threefold in APOC1 mice compared with wild-type mice (98 ± 21 vs 314 ± 88 ml ? kg-1 ? min-1, p < 0.05). Insulin-mediated whole body NEFA uptake, NEFA oxidation (generation of 3H2O) and NEFA storage were lower in APOC1 mice than in wild-type mice (15 ± 3 vs 33 ± 6; 3 ± 2 vs 11 ± 4 and 12 ± 2 vs 22 ± 4 μmol ? kg-1? min-1, p < 0.05) in the face of higher plasma NEFA concentrations (1.3 ± 0.3 vs 0.5 ± 0.1 mmol/l, p < 0.05), respectively. Mean arterial pressure and heart rate were similar in APOC1 vs wild-type mice (82 ±4 vs 85 ± 3 mm Hg and 459 ± 14 vs 484 ± 11 beats, min-1). Conclusions/interpretation. 1) Hyperlipidaemic APOC1 mice show reduced NEFA and increased glucose metabolism under both basal and insulin-mediated conditions, suggesting an intrinsic defect in NEFA metabolism. Primary hyperlipidaemia alone in APOC1 mice does not lead to insulin resistance for glucose metabolism and high blood pressure

Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues

Amylin is a polypeptide of 37 amino acids, predominantly synthesized in pancreatic Beta cells. The peptide was suggested to be dysregulated in Type 2 (non-insulin-dependent) diabetes mellitus and it antagonized certain actions of insulin in vitro in rat muscle. This led to speculation that amylin is involved in the pathogenesis of Type 2 diabetes. We have examined the in vivo effects of rat amylin, amidated at the carboxy-terminus, on insulin-mediated carbohydrate metabolism in conscious rats, using the hyperinsulinaemic (±1 nmol/l) euglycaemic (6 mmol/l) clamp technique combined with [3-3H]-glucose infusion. Basal plasma amylin levels were ≤75 pmol/l. Applied amylin levels of 220 ± 75 pmol/l (infusion rate of 12.5 pmol/min) antagonized only the insulin action on liver, resulting in a 100% increase of hepatic glucose output. Amylin levels of 4750 ± 750 pmol/l (infusion rate of 125 pmol/min) induced a 250% increase of insulin-inhibited hepatic glucose output and, in addition, a 30% decrease of insulin-stimulated peripheral glucose uptake. Amylin did not affect: 1) the metabolic clearance rate of insulin, 2) the levels of plasma glucagon, epinephrine, norepinephrine, and corticosterone, 3) in vitro insulin binding and insulin-stimulated receptor autophosphorylation. This suggests that amylin antagonizes insulin action via binding to a yet unknown receptor. In conclusion: amylin causes in vivo insulin resistance and the liver seems the predominant organ regulated by this hormone. The in vivo effects of amylin mimic the pathophysiological abnormalities of insulin action in Type 2 diabetes.