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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Today, obesity is the most important modifiable risk factor for type 2 diabetes. An excess of body fat is associated with a deterioration of glucose utilisation and promotes the development of type 2 diabetes, particularly in those with a genetic predisposition for the disease. It is also well established that a reduction of excess body fat improves insulin sensitivity and can prevent the conversion to diabetes. In those with overt diabetes, weight loss usually ameliorates glycaemic control and associated metabolic disturbances. Among the pharmacological agents that are used for the treatment of type 2 diabetes only metformin has a weak weight-lowering activity and is considered as the drug of choice for adjunct pharmacotherapy in obese diabetic subjects. A few studies also suggest that acarbose can induce a modest weight reduction in such patients. In contrast, sulphonylurea and insulin treatment is frequently accompanied by substantial weight gain which should be taken into consideration when these drugs are used. Another approach to improve metabolic control in obese type 2 diabetic patients is the use of weight-lowering agents. The new serotonin and noradrenaline reuptake inhibitor sibutramine promotes weight loss which subsequently leads to improved glycaemic control. Orlistat, a lipase inhibitor, is also able to ameliorate metabolic control in such patients due to its weight-lowering potential. As obesity remains a therapeutic challenge in most type 2 diabetic subjects, weight management drugs may represent an alternative or supplement to antidiabetic agents. Moreover, weight management agents have the advantage that they have additional favourable effects on associated cardiovascular risk factors.
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PMID:The impact of pharmacotherapy on weight management in type 2 diabetes. 1045 66

Hypertriglyceridaemia is thought to be the aetiology in 3% of patients with acute pancreatitis, often associated with poorly controlled diabetes mellitus or chronic alcohol abuse. However, in patients with non-biliary pancreatitis, chylomicronaemia is an underrated cause of acute pancreatitis. The activity of lipoprotein lipase (LPL) is crucial in removing triglycerides from the plasma; LPL gene mutations combined with secondary alterations in plasma lipoproteins, such as occur in pregnancy, diabetes mellitus, and alcohol abuse can cause severe hypertriglyceridaemia and pancreatitis. Heparin and insulin stimulate LPL activity. During a 12 months' period we consecutively screened all patients with the diagnosis of acute non-biliary pancreatitis for hypertriglyceridaemia, to evaluate the prevalence of hypertriglyceridaemia-induced pancreatitis and to assess the outcome under standardised treatment with intravenous heparin and insulin. Hypertriglyceridaemia-induced pancreatitis was diagnosed in 5 out of 46 patients (11%) with acute pancreatitis. In 2 patients hypertriglyceridaemia was associated with diabetes mellitus, in one patient with pregnancy and in another with chronic alcohol abuse. Four patients had to be referred to the intensive care unit. Plasma concentrations of triglycerides were (median +/- range) 43 mmol/l (14.7 to 80.4); pancreas amylase was 574 U/l (155 to 1606), and lipase was 1003 U/l (330 to 3010). All patients had oedematous pancreatitis demonstrated by CT scan. Treatment with i.v. heparin and i.v. insulin decreased trigylceride levels to less than 10 mmol/l within 2.8 days (1 to 6), the amylase and lipase levels returned to normal after 3 and 4 days respectively, and the abdominal pain was resolved. Hypertriglyceridaemia is a common and under-diagnosed etiology of acute non-biliary pancreatitis. Intravenous heparin and insulin is safe and effective in the treatment of hypertriglyceridaemia-induced pancreatitis. Low fat diet, supplements of (n-3) fatty acids ("fish oil") and fibrates are recommended for long-term maintenance therapy.
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PMID:[Heparin and insulin in the treatment of acute hypertriglyceridemia-induced pancreatitis]. 1049 50

Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. In the majority of cases, particularly in Western populations, the disease is associated with alcohol abuse. The major complications of chronic pancreatitis include abdominal pain, malabsorption, and diabetes. Of these, pain is the most difficult to treat and is therefore the most frustrating symptom for both the patient and the physician. While analgesics form the cornerstone of pain therapy, a number of other treatment modalities (inhibition of pancreatic secretion, antioxidants, and surgery) have also been described. Unfortunately, the efficacy of these modalities is difficult to assess, principally because of the lack of properly controlled clinical trials. Replacement of pancreatic enzymes (particularly lipase) in the gut is the mainstay of treatment for malabsorption; the recent discovery of a bacterial lipase (with high lipolytic activity and resistance to degradation in gastric and duodenal juice) represents an important advance that may significantly increase the efficacy of enzyme replacement therapy by replacing the easily degradable porcine lipase found in existing enzyme preparations. Diabetes secondary to chronic pancreatitis is difficult to control and its course is often complicated by hypoglycaemic attacks. Therefore, it is essential that caution is exercised when treating this condition with insulin. This paper reviews recent research and prevailing concepts regarding the three major complications of chronic pancreatitis noted above. A comprehensive discussion of current opinion on clinical issues relating to the other known complications of chronic pancreatitis such as pseudocysts, venous thromboses, biliary and duodenal obstruction, biliary cirrhosis, and pancreatic cancer is also presented.
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PMID:Chronic pancreatitis: complications and management. 1050 49

Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.
Diabetes Res Clin Pract 1999 Nov
PMID:The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase. 1072 87

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered as a key objective. In this respect, several antiobesity drugs have demonstrated potential. However, while fenfluramine and dexfenfluramine have been shown to promote weight loss and to directly improve insulin sensitivity, being two mechanisms contributing to better blood glucose control in obese Type 2 diabetic patients, they were recently withdrawn due to safety problems. Sibutramine, a new selective norepinephrine and serotonin reuptake inhibitor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing > or =5% of initial body weight) of blood glucose control in obese diabetic patients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especially dyslipidaemia, in obese Type 2 diabetic patients. Further studies are required to better identify good responders to pharmacotherapy and specify the role of antiobesity agents in the overall long-term management of obese subjects with Type 2 diabetes. Other novel pharmacological approaches deserve further consideration, for instance beta-3 agonists aiming to increase energy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-alpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or safety have been disappointing or preliminary in humans.
Diabetes Metab Res Rev
PMID:Antiobesity pharmacotherapy in the management of type 2 diabetes. 1075 51

Current agents for the treatment of Type 2 diabetes mellitus improve the metabolic profile but do not reinstate normality. They also reduce chronic diabetic complications, but they do not eliminate them. Thus, new agents with novel actions are required to complement and extend the capabilities of existing treatments. Insulin resistance and beta-cell failure, which are crucial components in the pathogenesis of Type 2 diabetes, remain the underlying targets for new drugs. Recently introduced agents include a short-acting non-sulphonylurea insulin-releaser, repaglinide, which synchronizes insulin secretion with meal digestion in order to reduce post-prandial hyperglycaemia. The thiazolidinedione drugs, troglitazone, rosiglitazone and pioglitazone represent a new class of agonists for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma). PPARgamma increases the transcription of certain insulin-sensitive genes, thereby improving insulin sensitivity. The intestinal lipase inhibitor orlistat and the satiety-inducer sibutramine are new weight-reducing agents that may benefit glycaemic control in obese Type 2 diabetes patients. Several further new insulin-releasing agents, and agents to retard carbohydrate digestion and modify lipid metabolism stand poised to enter the market. The extent to which they will benefit glycaemic control remains to be seen. However, the prospect of permanently arresting or reversing the progressive deterioration of Type 2 diabetes continues to evade therapeutic capture.
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PMID:New agents for Type 2 diabetes. 1076 69

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum nonesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similarly shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum-FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisons in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin deficiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizing glyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses. Results are discussed on the basis of interactions of serum NEFAs and FG with respective blood sugar and serum immunoreactive insulin levels as influenced by DM and estrous cycle.
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PMID:Natural estrous cycle in normal and diabetic bitches. II). Serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests. 1079 39

The medical treatment has an important role in patients with chronic pancreatitis. Pain is the most frequent symptom, at least in the initial phases of the disease. In about 60% of patients it can be successfully treated by medical therapy; in the remaining 40% it requires surgery. Malabsorption of fat and protein and diabetes usually appear in the advanced stages of the disease. The treatment of these complications is based on the administration of pancreatic extracts and insulin. There are several types of pancreatic extracts; the most useful are those with high lipase content and high lipase-protease ratio. Moreover, they should be protected against gastric acid and should have a gastric emptying simultaneously with chyme, with a rapid liberation of enzymes into the duodenum. The treatment of diabetes usually requires low-moderate doses of insulin. Diabetic ketoacidosis is rare, while microvascular changes have the same frequency as in type 1 diabetes.
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PMID:Medical treatment of chronic pancreatitis. 1082 21

We used wild-type (WT) mice and mice engineered to express either apoB-100 only (B100 mice) or apoB-48 only (B48 mice) to examine the effects of streptozotocin-induced diabetes (DM) on apoB-100- and apoB-48-containing lipoproteins. Plasma lipids increased with DM in WT mice, and fat tolerance was markedly impaired. Lipoprotein profiles showed increased levels and cholesterol enrichment of VLDL in diabetic B48 mice but not in B100 mice. C apolipoproteins, in particular apoC-I in VLDL, were increased. To investigate the basis of the increase in apoB-48 lipoproteins in streptozotocin-treated animals, we characterized several parameters of lipoprotein metabolism. Triglyceride and apoB production rates were normal, as were plasma lipase activity, VLDL glycosaminoglycan binding, and VLDL lipolysis. However, beta-VLDL clearance decreased due to decreased trapping by the liver. Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls. Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG. Western blots of livers from diabetic mice showed a decrease in the HSPG core protein, perlecan. Delayed clearance of postprandial apoB-48-containing lipoproteins in DM appears to be due to decreased hepatic perlecan HSPG.
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PMID:Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. 1086 96

During late gestation, although maternal adipose tissue lipolytic activity becomes enhanced, lipolytic products cross the placenta with difficulty. Under fasting conditions, free fatty acids (FFA) are used for ketogenesis by the mother, and ketone bodies are used as fuels and lipogenic substrates by the fetus. Maternal glycerol is preferentially used for glucose synthesis, saving other gluconeogenic substrates, like amino acids, for fetal growth. Placental transfer of triglycerides is null, but essential fatty acids derived from maternal diet, which are transported as triglycerides in lipoproteins, become available to the fetus owing to the presence of both lipoprotein receptors and lipase activities in the placenta. Diabetes in pregnancy promotes lipid transfer to the fetus by increasing the maternal-fetal gradient, which may contribute to an increase in body fat mass in newborns of diabetic women. Deposition of fat stores in the fetus is very low in the rat but high in humans, where body fat accretion occurs essentially during the last trimester of intra-uterine life. This is sustained by the intense placental transfer of glucose and by its use as a lipogenic substrate, as well as by the placental transfer of fatty acids and to their low oxidation activity. During the perinatal period an active ketonemia develops, which is maintained in the suckling newborn by several factors: (i) the high-fat and low-carbohydrate content in milk, (ii) the enhanced lipolytic activity occurring during the first few hours of life, and (iii) both the uptake of circulating triglycerides by the liver due to the induction of lipoprotein lipase (LPL) activity in this organ, and the presence of ketogenic activity in the intestinal mucose. Changes in LPL activity, lipogenesis and lipolysis contribute to the sequential steps of adipocyte hyperplasia and hypertrophia occurring during the extra-uterine white adipose tissue development in rat, and this may be used as a model to extrapolate the intra-uterine adipose tissue development in other species, including humans.
Diabetes Metab Res Rev
PMID:Lipid metabolism in the fetus and the newborn. 1086 20


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