Obesity: Gudbjörnsdottir S

Gudbjörnsdottir S, Eeg-Olofsson K, Cederholm J, Zethelius B, Eliasson B, Nilsson PM, Anonymous00042. · Department of Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden. · Diabet Med. · Pubmed #19125761 No free full text.

Abstract: AIMS: Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. METHODS: This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). RESULTS: In patients with CHD 1-2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA(1c) < 7%, 47%/54% (P < 0.01); blood pressure < or = 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) > or = 25 kg/m(2)], 86%/85%; obesity (BMI > or = 30 kg/m(2)), 41%/42%; smokers in age group < 65 years, 16-23%/18-19%; as well as waist circumference > or = 102 cm (men) or > or = 88 cm (women), 68% in 2005. CONCLUSIONS: Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients.

Eliasson B, Gudbjörnsdottir S, Cederholm J, Liang Y, Vercruysse F, Smith U. · Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden. bjorn.eliasson@gu,se · Int J Obes (Lond). · Pubmed #17264849 No free full text.

Abstract: OBJECTIVE: To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months. DESIGN AND SUBJECTS: Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase). MEASUREMENTS: Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion. RESULTS: The mean age was 58.6+/-7.1 years, body weight 98.1+/-16.1 kg, BMI 33.0+/-4.5 kg/m(2), and glycosylated hemoglobin (HbA1c) 7.3+/-0.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.1+/-0.9%), fasting plasma glucose, body weight (-6.6+/-3.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate. CONCLUSIONS: Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

Ridderstråle M, Gudbjörnsdottir S, Eliasson B, Nilsson PM, Cederholm J, Anonymous00046. · Department of Clinical Sciences, Clinical Obesity, Lund University, Wallenberg Laboratory, University Hospital, Malmö, Sweden. · J Intern Med. · Pubmed #16476109 No free full text.

Abstract: OBJECTIVES: To compare obese with normal and overweight type 2 diabetic patients regarding body mass index (BMI) and cardiovascular risk factors, and to analyse changes in weight versus risk factors. DESIGN AND SETTING: A cross-sectional study of 44 042 type 2 patients, and a 6-year prospective study of 4468 type 2 patients. RESULTS: Obese patients (BMI > or = 30 kg m(-2)), 37% of all patients, had high frequencies of hypertension (88%), hyperlipidaemia (81%) and microalbuminuria (29%). Only 11% had blood pressure <130/80 mmHg. Their ratio of triglycerides to HDL cholesterol was considerably elevated, whilst the mean total and LDL cholesterol were similar as in normal weight subjects. Obese patients had elevated odds ratios for hypertension, hyperlipidaemia and microalbuminuria: 2.1, 1.8 and 1.4 in the cross-sectional study, similarly confirmed in the prospective 6-year study. BMI was an independent predictor of these risk factors (P < 0.001), although only slightly associated with HbA1c and not with total or LDL cholesterol. A change in BMI during the prospective study was related to a change in HbA1c in patients treated with diet and oral hypoglycaemic agents (OHAs) but not with insulin. In all patients, an increase in BMI was related to the development of hypertension, and a change in BMI to change in blood pressure, also mostly confirmed when treated with diet, OHAs or insulin. CONCLUSIONS: The high frequencies of risk factors in obese type 2 patients implies an increased risk of cardiovascular disease and the need for therapeutic measures. The paradox that hypoglycaemic treatment accompanied by weight gain may increase cardiovascular risk factors seems to be verified here concerning hypertension but not concerning microalbuminuria.

Gudbjörnsdottir S, Cederholm J, Nilsson PM, Eliasson B, Anonymous00032. · Diabetes Centre, Sahlgrenska University Hospital, Göteborg, Sweden. · Diabetes Care. · Pubmed #12663609 links to  free full text

Abstract: OBJECTIVE: To monitor glycemic control, treatable risk factors, and treatment profile for quality assessment of diabetes care on a national scale. RESEARCH DESIGN AND METHODS: Four samples of 23,546, 32,903, 30,311, and 29,769 patients with diabetes (1996-1999) were studied based on a repeated national screening and quality assessment of diabetes care by the National Diabetes Register, Sweden, with participation of both hospitals and primary health care. Clinical characteristics included were age, sex, diabetes duration and treatment, glycemic control (HbA(1c)), office blood pressure (BP), BMI, smoking habits, and use of lipid-lowering drugs in patients with type 1 or type 2 diabetes. RESULTS: Favorable decreases of mean HbA(1c) and BP values were registered during the 4-year study period for both type 1 (HbA(1c) 7.5-7.3% and BP 130/75-130/74 mmHg) and type 2 diabetic patients (HbA(1c) 7.0-6.7% and BP 151/82-147/80 mmHg). Treatment aims of HbA(1c) and BP levels were also achieved in increasing proportions for type 1 (HbA(1c) <7.5%: 50-58% and BP </=140/85 mmHg: 77-79%), and type 2 diabetic patients (HbA(1c) <7.5%: 66-73% and BP </=140/85 mmHg: 32-42%). The use of lipid-lowering drugs increased for type 1 (4-11%) and type 2 diabetic patients (10-22%). In type 2 diabetic patients, treatment with oral agents alone decreased, but combination therapy (insulin and oral agents) increased during the study period. Mean BMI increased during 1996-1999 in type 2 diabetic patients. High HbA(1c) and BP values in 1999 were predicted by high BMI values 1996 and by high increase of BMI during the period, independent of diabetes duration, age, and sex. CONCLUSIONS: Decreasing mean HbA(1c) and BP levels and the wider use of lipid-lowering drugs during the late 1990s in patients with diabetes in a national sample from Sweden should translate into clinical benefits regarding micro- and macrovascular complications as well as diabetes-related mortality.

Sjöstrand M, Gudbjörnsdottir S, Holmäng A, Lönn L, Strindberg L, Lönnroth P. · Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden. · Diabetes. · Pubmed #12196467 links to  free full text

Abstract: Insulin-resistant subjects have a slow onset of insulin action, and the underlying mechanism has not been determined. To evaluate whether a delayed transcapillary transport is part of the peripheral insulin resistance, we followed the kinetics of infused insulin and inulin in plasma and muscle interstitial fluid in obese insulin-resistant patients and control subjects. A total of 10 lean and 10 obese men (BMI 24 +/- 0.8 vs. 32 +/- 0.8 kg/m(2), P < 0.001) was evaluated during a hyperinsulinemic-euglycemic clamp (insulin infusion rate 120 mU. m(-2). min(-1)) combined with an inulin infusion. Measurements of insulin and inulin in plasma were taken by means of arterial-venous catheterization of the forearm and microdialysis in brachioradialis muscle combined with forearm blood flow measurements with vein occlusion pletysmography. The obese subjects had a significantly lower steady-state glucose infusion rate and, moreover, demonstrated a delayed appearance of insulin (time to achieve half-maximal concentration [T(1/2)] 72 +/- 6 vs. 46 +/- 6 min in control subjects, P < 0.05) as well as inulin (T(1/2) 83 +/- 3 vs. 53 +/- 7 min, P < 0.01) in the interstitial fluid. Also, the obese subjects had a delayed onset of insulin action (T(1/2) 70 +/- 9 vs. 45 +/- 5 min in control subjects, P < 0.05), and their forearm blood flow rate was significantly lower. These results demonstrate a delayed transcapillary transport of insulin and inulin from plasma to the muscle interstitial fluid and a delayed onset of insulin action in insulin-resistant obese subjects.

Sjöstrand M, Gudbjörnsdottir S, Holmäng A, Strindberg L, Ekberg K, Lönnroth P. · Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg S-413 45, Sweden. · J Clin Endocrinol Metab. · Pubmed #11994365 links to  free full text

Abstract: The aim of this project was to study the regulation of interstitial glycerol levels in muscle in normal subjects, and to estimate interstitial muscle glycerol in obese subjects and patients with type 2 diabetes. In healthy lean subjects, microdialysis of forearm sc and muscle tissue were combined with arterial and deep venous catheterization, as well as blood flow registrations during oral glucose ingestion. In two other separate studies, obese (n = 9) vs. lean (n = 10) subjects and type 2 diabetes patients (n = 8) vs. weight-matched control subjects (n = 8) were investigated by means of muscle microdialysis during a euglycemic hyperinsulinemic clamp. Oral glucose ingestion suppressed the interstitial sc glycerol concentration by approximately 40% (P < 0.05), whereas no significant reduction of muscle interstitial glycerol was found. In contrast to the significant muscle interstitial-arterial (I-A) glycerol difference, the venous-arterial difference was small and varying throughout the oral glucose tolerance test. At steady-state hyperinsulinemia, obese subjects' interstitial muscle glycerol and I-A glycerol difference were both significantly higher than lean controls, whereas type 2 diabetes patient had interstitial muscle glycerol concentrations and I-A glycerol differences similar to those found in weight-matched controls. A significant and marked I-A glycerol difference exists in the absence of a significant venous-arterial difference, indicating that muscle glycerol cannot be taken as a marker of intramyocellular lipolysis because local turnover of muscle glycerol might be significant. The present data also suggest that, in contrast to sc tissue, muscle tissue lacks a clear antilipolytic effect of insulin. Moreover, the muscle interstitial glycerol concentration is elevated in obese patients but does not precipitate insulin resistance and type 2 diabetes.

Sjöstrand M, Gudbjörnsdottir S, Strindberg L, Lönnroth P. · Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden. · Diabetes. · Pubmed #15616023 links to  free full text

Abstract: Obese subjects exhibit a delay in insulin action and delivery of insulin to muscle interstitial fluid during glucose/insulin infusion. The aim of the present study was to follow the distribution of insulin to skeletal muscle after an oral glucose load in obese subjects. We conducted an oral glucose tolerance test (OGTT) in 10 lean and 10 obese subjects (BMI 23 +/- 0.6 vs. 33 +/- 1.2 kg/m(2); P < 0.001). Insulin measurements in muscle interstitial fluid were combined with forearm arteriovenous catheterization and blood flow measurements. In the obese group, interstitial insulin was significantly (35-55%) lower than plasma insulin (P < 0.05) during the 1st h after the OGTT, whereas in lean subjects, no significant difference was found between interstitial and plasma insulin levels during the same time period. The permeability surface area product for glucose, representing capillary recruitment, increased in the lean group (P < 0.05) but not in the obese group (NS). Obese subjects had a significantly higher plasma insulin level at 90-120 min after oral glucose (398 +/- 57 vs. 224 +/- 37 pmol/l in control subjects; P < 0.05). The significant gradient between plasma insulin and muscle interstitial insulin during the first hour after OGTT suggests a slow delivery of insulin in obese subjects. The hindered transcapillary transport of insulin may be attributable to a defect in insulin-mediated capillary recruitment.