Worsening Of Glycemic Control Research Articles

Fasting Hyperglucagonemia in Patients with Transjugular Intrahepatic Portosystemic Shunts (TIPS)

Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.

Psychosocial Predictors of Relapse Among Diabetes Patients: A 2-Year Follow-Up After Inpatient Diabetes Education

In a 2-year follow-up study of diabetes patients (N=309) who received 2 weeks of inpatient diabetes education, the authors investigate the relationship of several demographic, clinical, and psychosocial factors with relapse, defined as the worsening of glycemic control. The patients with no improvement in glycemic control after diabetes education were more likely to have higher scores on the depression subscale of the Profile of Mood States, compared to the patients with improvement. Kaplan-Meier survival analyses showed that patients who had no prior diabetes education, whose meals were prepared by their spouses, and who had less social support were more likely to relapse and relapsed within a significantly shorter period of time than those who had prior diabetes education, cooked for themselves, and had more social support.

Hyperglucagonemia in patients with transjugular intrahepatic portosystemic stent-shunts (TIPS)

Background: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic stent-shunts (TIPS). Methods: Glucagon, plasma glucose, HbA1c, C-peptide and insulin were determined in peripheral venous samples from 21 diabetic (D)- and 15 non-diabetic patients (ND; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with comparable clinical features (age, BMI, Child-Pugh-score, creatinine) before, 3 and 9 months after TIPS implantation. Results: Glucogon levels before TIPS were elevated in diabetics compared to non-diabetics (D: 145,4±52,1 vs. ND: 97,3±49,8 pg/ml; p=0,057). Three and nine months after TIPS implantation glucagon levels increased significantly in ND (183,9±80,3 and 176,2±93,4 pg/ml) but not in D (169,0±62,4 and 171,9±58,4 pg/ml). While plasma glucose, HbA1c and C-peptide were significantly higher in D than in ND, they did not change significantly three and nine months after TIPS implantation. Insulin was increased in D before TIPS (D: 31,8±15,9 vs. ND: 14,8±7,1 mU/l; p=0,0001). Three and nine months after TIPS insulin significantly increased in ND (26,6±14,7 and 23,2±10,9 vs. 14,8±7,1 mU/l before TIPS) but not in D. Liver and kidney function did not change with time. Conclusions: In non-diabetic cirrhotic patients TIPS implantation is followed by a significant increase of plasma glucagon. However this does not result in a worsening of glycemic control, apparently because of a simultaneous increase of insulin.

Combination Therapies With Insulin in Type 2 Diabetes

The U.K. Prospective Diabetes Study (UKPDS) demonstrated that intensive glucose control with insulin or sulfonylureas markedly reduces the risk of microvascular complications (1). For myocardial infarction, the reduction in risk (16% for a 0.9% decrease in HbA1c) was of borderline significance but corresponded closely to epidemiological predictions (14% decrease for a 1% drop in HbA1c) (2). These data demonstrated that neither insulin nor sulfonylureas, despite causing hyperinsulinemia and weight gain, have adverse effects on cardiovascular outcome. Glycemic control deteriorated continuously, however, even in intensively treated patients in the UKPDS (1). In the UKPDS, the worsening of glycemic control has been attributed to the natural course of type 2 diabetes and lack of efficacy of current antihyperglycemic therapies (1). Insulin therapy consisted of a single injection of ultralente or isophane insulin. If the daily dose exceeded 14 U, regular insulin was added and home-glucose monitoring was encouraged (1). Combination therapy regimens with insulin and oral agents were not used. We now know that 14 U of long-acting insulin is insufficient to control fasting glycemia in most type 2 diabetic patients (3). Since 1977, when the UKPDS was started, several studies have tried to define the optimal insulin treatment regimen for type 2 diabetic patients. These studies are the focus of this review and include studies comparing insulin alone to combination therapy with insulin and sulfonylureas (subject to meta-analyses in 1991 and 1992) (4,5) and more recent trials using metformin, glitazones, or acarbose in insulin combination therapy regimens. They do not contain data on cardiovascular end points but only on surrogate markers of risk of micro- and macrovascular complications, mostly data on glycemia, body weight, insulin doses, lipids, and in a few studies, also accurate data on the frequency of hypoglycemias. According to a Medline search (1966–2000), …

Special considerations in the therapy of diabetic hypertension

Patients with diabetes mellitus have an increased prevalence of hypertension and associated cardiovascular disease (CVD), including coronary and cerebrovascular disease. The risk of an individual of developing CVD is much greater when both diseases coexist and is further magnified by their frequent association with dyslipidemia, coagulation, platelet, and endothelial abnormalities. Metabolic abnormalities frequently associated with hypertension are insulin resistance, enhanced coagulation, and decreased fibrinolytic activity. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including altered efficacy of medications, possible side effects, worsening of glycemic control, and impairment of lipid metabolism. Because hypertension is a major contributor to morbidity and mortality in diabetes, it should be recognized and treated early and aggressively despite these difficulties. This article reviews the efficacy and side effects of the various classes of antihypertensive agents in patients with diabetes mellitus. Copyright © 1999 by W.B. Saunders Company Progress in Cardiovascular Diseases, Vol. 41, No. 6 (May/June), 1999: pp 461-470

N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter Study

A multicenter, randomized, double-blind, place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes. A total of 935 patients of both sexes in 63 Italian clinical centers were selected; 55% had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus (NIDDM). They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo, followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo. In addition to the complete lipid and lipoprotein evaluation, patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test; in patients with NIDDM, serum insulin and glycated hemoglobin (Hb A1c) concentrations were determined. Plasma triacylglycerol concentrations decreased significantly, up to 21.53% at 6 mo compared with baseline (decreased 15% compared with placebo), with a tendency toward a progressive reduction with time. There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance. Among NIDDM patients, the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes: fasting glucose, Hb A1c, insulinemia, and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters. Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation.

Lipids and lipoproteins as risk factors for coronary heart disease in non-insulin-dependent diabetes mellitus.

Dyslipidaemia is frequent in non-insulin-dependent diabetes mellitus (NIDDM). Lipid and lipoprotein abnormalities include particularly elevated levels of total and very-low-density lipoprotein (VLDL) triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. The worsening of glycaemic control further deteriorates lipid and lipoprotein abnormalities and furthermore, total and low-density lipoprotein (LDL) cholesterol levels are often elevated in poor glycaemic control. Epidemiological data show that total cholesterol is as powerful risk factor for coronary heart disease (CHD) in NIDDM patients as in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in NIDDM patients than in nondiabetic individuals, but more prospective studies are needed to substantiate this view. Compositional changes in LDL and VLDL particles may further increase the risk of CHD but epidemiological data are missing to support this notion.

Glycaemia and body mass as determinants of plasma lecithin: cholesterol acyltransferase activity in Nigerian patients with non-insulin dependent diabetes mellitus

There is an inverse correlation between plasma high density lipoprotein (HDL) concentrations and atherogenic vascular morbidity risk. An important pathway for modulating circulating HDL levels is the reaction catalysed by the plasma enzyme, lecithin:cholesterol acyltransferase (LCAT). Thus, determinants of LCAT activity should influence plasma HDL levels and be accessible targets for intervention. We therefore assessed such determinants in Nigerian patients with non-insulin dependent diabetes mellitus (NIDDM), classified into age-and sex-matched groups of obese (body mass index, BMI, > 25 kg/m 2) and non-obese (BMI < 25 kg/m 2). Our results indicated that 10 obese diabetic patients had significantly reduced plasma LCAT activity and HDL levels and increased plasma triglyceride (TG) levels, in comparison with the observations in 9 non-obese diabetic patients (all P < 0.05). Furthermore, worsening of glycaemic control, when oral hypoglycaemic treatment was discontinued for 1 week in 10 diabetic (5 obese) patients, further reduced fasting levels of HDL and plasma LCAT activity (both P < 0.05). Although plasma HDL concentrations and LCAT activity levels did not correlate significantly, the latter nonetheless had a significant inverse relationship with fasting plasma glucose levels in the obese diabetic subjects ( r−0.51, P < 0.05). These results indicate that glycaemia and body mass are important determinants of plasma LCAT activity. Both variables are subject to pharmacological and dietary intervention with the objective of increasing circulating HDL levels.