Relationship between diurnal glucose levels and HbA1c in type 2 diabetes.

AIMS AND METHODS: Study results still conflict on the contribution of diurnal blood glucose (BG) values to Hb (A1c) in type 2 diabetes. We investigated the relationship between Hb (A1c) and diurnal BG obtained under standardized conditions - before breakfast, two hours after breakfast, before lunch, two hours after lunch, before dinner, two hours after dinner, and at 10 PM, 12 midnight and 3 AM in 68 type 2 diabetic patients before and after optimizing glycemic control. The areas under the curve above fasting BG (AUC1) and above 5.6 mmol/l (AUC2) were calculated for further evaluation. Hb (A1c) was measured at baseline and after a mean of 89 (74 to 108) days. RESULTS: Each BG value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. The pre-breakfast BG showed the closest correlation with Hb (A1c). The relative contribution of postprandial BG concentrations (AUC1) to overall hyperglycemia (AUC2) decreased with poorer glycemic control. However, treatment optimization mainly resulted in improved blood glucose values in patients with the poorest glycemic control at baseline. Multiple regression analysis demonstrated that fasting (AUC2-AUC1) and postprandial (AUC1) hyperglycemia independently determined Hb (A1c) or the change in Hb (A1c) after treatment optimization. CONCLUSIONS: Our findings indicate that intensive blood glucose monitoring during fasting and postprandial states is important for glycemic control, and is therefore an essential part of good clinical practice.

[Indications for the surgical therapy of obesity with magenband operation (gastric banding)]. / Indikation zur chirurgischen Therapie der Adipositas mit der Magenband-Operation (Gastric Banding).

Morbid obesity is an increasing problem in most of the industrial countries. Conservative treatment strategies are often not very effective. Because of the enormous costs and concomitant diseases of obesity, effective therapeutic strategies are mandatory. Gastric banding is a surgical method to reduce weight in the long run when patients are morbidly obese. A silicone band is used to create a small pouch in the upper part of the stomach leading to early satiety after ingestion only small amounts of food. The benefit of this method is the laparoscopic technique and the reversibility, because the band is easy to remove. In the long run a significant reduction of weight and an amelioration or even prevention of diseases resulting from obesity can be achieved. To assure treatment quality, it makes sense to administer this therapy in an interdisciplinary setting that integrates psychosomatic diagnostics and therapies, too. This paper reviews indications, contraindications as well as pre- and postoperative necessarily care of gastric banding.

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients.

AIM: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. METHODS: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m2), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose (n = 25) or 1 mg t.i.d. glibenclamide (n = 27) or one t.i.d. placebo (n = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test. RESULTS: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0]. CONCLUSIONS: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.

Different effects of acarbose and glibenclamide on proinsulin and insulin profiles in people with Type 2 diabetes.

AIM: In a double-blind, placebo-controlled study, we compared the effect of acarbose (A) and glibenclamide (G) on post-prandial (pp) and 24-h profiles of proinsulin and insulin. METHODS: Twenty-seven patients with Type 2 diabetes mellitus insufficiently controlled with diet alone were randomised to receive acarbose, 100 mg thrice daily, glibenclamide, 1 mg thrice daily, or placebo. Before and after 16 weeks of treatment, 24-h profiles of proinsulin, insulin and glucose (fasting, 1 h after breakfast and every 3-h for a 24-h period) were measured under metabolic ward conditions with standardised meals. RESULTS: With acarbose, a reduced 24-h level of proinsulin was observed compared with glibenclamide (AUC 1096 +/- 118 vs. 1604 +/- 174 pmol/l per h, P<0.05) at 16 weeks. The breakfast increment of proinsulin was lower with acarbose than glibenclamide (6.8 vs. 19.3 pmol/l, P<0.05) as was the level at that time (37.3 +/- 5.3 vs. 56.4 +/- 7.5 pmol/l, P<0.05). A lower AUC of insulin after treatment was also observed with acarbose than glibenclamide (7.9 +/- 0.9 vs. 14.8 +/- 4.5 nmol/l per h, P<0.05), as also for 1-h increment (81 +/- 26, vs. 380 +/- 120 pmol/l, P<0.01) and 1-h level (325 +/- 30 vs. 621 +/- 132 pmol/l, P<0.01). Acarbose reduced 1-h breakfast glucose increment (baseline 6.3 +/- 0.6, 16-week 3.5 +/- 0.6 mmol/l, P<0.01) and 1-h glucose level (18.1 +/- 1.1 and 14.5 +/- 1.3 mmol/l, P<0.01), whereas glibenclamide did not (6.6 +/- 0.7 vs. 5.4 +/- 0.6 mmol/l and 18.9 +/- 1.5 vs. 15.3 +/- 1.3 mmol/l). CONCLUSIONS: Measurement of circadian excursions of proinsulin and insulin reveals distinct differences in meal-time proinsulin and insulin increment and level between acarbose and glibenclamide whereas fasting levels of these insulin fractions remained unaffected.

[An unusual picture of insulinoma in type-2 diabetes mellitus and morbid obesity]. / Ungewöhnliches Bild eines Insulinoms bei Diabetes mellitus Typ 2 und morbider Adipositas.

HISTORY AND CLINICAL FINDINGS: Marked hyperinsulinism was demonstrated in the course of an oral glucose tolerance test (oGTT) in a 63-year-old woman with severe obesity (height 1.59 m, body weight 123 kg, body-mass index 46.4 kg/m2). The diabetic metabolic state, first diagnosed 12 years ago, had been replaced by a low plasma glucose level: she often had attacks of ravenous hunger. A reducing diet of 800 kcal had not been tolerated. She had not had any syncopes. She had continually gained weight since puberty, but her weight had remained relatively constant for the past 5 years during which she had been treated with L-thyroxine for a diffuse goitre (stage II). INVESTIGATIONS: In the course of an oGTT (75 g glucose) the basal insulin concentration (146 pmol/l) had risen to 1663 pmol/l at 30 min. The basal proinsulin level was 50 times normal (66 pmol/l vs. 1.418 pmol/l), while the initial plasma glucose level had fallen from 4.3 mmol/l to 3.8 mmol/l. Spiral computed tomography of the pancreas showed a 3 x 2.5 cm mass in the region of the tail of the pancreas. TREATMENT AND COURSE: At laparoscopy a 4 cm tumor was palpated in the region of the pancreatic tail. Left resection of the pancreas was performed. Histopathological examination of the surgical specimen confirmed an insulinoma. A repeat of oGTT 6 months postoperatively demonstrated a markedly diminished insulin level compared with the preoperative results, as well as a diabetic metabolic state. CONCLUSION: In case of dramatic improvement of diabetes mellitus in an obese patient without drug treatment or weight reduction an insulin-producing tumour should be considered in the differential diagnosis. There may be no typical hypoglycaemic symptoms because of insulin resistance associated with the obesity.

Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I.

The influence of hGH and IGF-I levels on lipid-, lipoprotein metabolism and fibrinolysis were studied in 23 patients with active acromegaly (14 women and 9 men, mean age 49.8 +/- 2.1 years) compared to a sex, BMI and age-matched control group. Mean Lp(a) levels were significantly higher in acromegalics than in controls (469.8 +/- 140.1; n = 23 vs. 162.7 +/- 64.9 mg/l; n = 111; p < 0.01). We found elevated apolipoprotein A-I and Apo E-concentrations in acromegalic patients compared to controls (apo A-I: 1.79 +/- 0.06 vs. 1.46 +/- 0.04 g/l; p < 0.01; apo E: 98.35 +/- 6.4 vs. 72.53 +/- 3.38 mg/l; p < 0.05). 30% of the acromegalics showed increased plasminogen activator inhibitor activity (PAI) while 66% had increased tissue-type plasminogen activator (t-PA) concentrations. There was a correlation between hGH and Lp(a) (r = 0.414; p = 0.05), between hGH and PAI (r = -0.59; p < 0.005) and IGF-I and t-PA activity (r = -0.44; p < 0.05). In a subgroup of nine acromegalics Lp(a) was reduced by 32.2 +/- 6.7% (p < 0.05) after a six-month octreotide therapy and HDL2-cholesterol-concentration increased from 0.17 +/- 0.04 to 0.24 +/- 0.04 mmol/l (p < 0.05). In conclusion, our results demonstrate that elevated Lp(a)-concentrations and changes in fibrinolysis contribute to the cardiovascular complications and should therefore be controlled in acromegalic patients.

Long-term effect of octreotide in acromegaly on insulin resistance.

An important feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucosal disposal. Octreotide (SMS) exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. Eight patients with active acromegaly despite surgical intervention (age 44.8 +/- 3.5 years, BMI 27.3 +/- 1.6 kg/m2, lean body mass (LBM) 70 +/- 3.2%, blood glucose 5.24 +/- 0.26 mmol/l, HbA1c < or = 6.5%) were investigated before and after 6 months of treatment with SMS in an open trial. SMS was injected sc. at a dosage between 100-200 micrograms t.i.d. Mean GH and IGF1 levels during SMS therapy were significantly reduced (GH 9.6 +/- 1.9 ng/ml vs. 4.9 +/- 1.3 ng/ml, p < 0.05; IGF1 729.5 +/- 84 ng/ml vs. 415 +/- 49 ng/ml, p < 0.05). OGTT and euglycaemic-clamp-studies were performed before and after 6 months of SMS treatment. The glucosal disposal rate on average (insulin infusion rate 40 mU/m2/min) was not significantly changed following SMS treatment (McLBM before 3.60 +/- 0.38, after 3.95 +/- 0.41 mg/kg LBM/min). There was a positive correlation (r = 0.620) between the individual change of IGF1 and the change of McLBM. Additionally there was no significant difference of serum basal insulin levels (0.19 +/- 0.01 vs. 0.23 +/- 0.06 nmol/l) as well as basal C-peptide levels (0.79 +/- 0.07 vs. 0.47 +/- 0.04 nmol/l) before and with SMS treatment. We therefore conclude that long-term treatment of acromegalic patients with SMS, which achieves a successful reduction of GH and IGF1 levels, does not always guarantee a significant improvement in glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)