Glucose tolerance disorders in patients with cancer of the colon

Relating to the Williams' report suggesting twofold higher incidence of diabetes mellitus in patients with the cancer of the colon, the study aiming at comparing an incidence of diabetes mellitus in patients with stomach, lung, and colon malignancies were carried out. Coexistence of the above listed neoplasms with diabetes mellitus type II was assessed in patients hospitalized at the Department of Gastroenterology and Metabolic Diseases, Institute of the Internal Diseases, Medical Academy in Warsaw within 1978-1986. Moreover, glycaemia and insulinemia curves were plotted following oral glucose load (75 g) in 16 patients with the cancer of the colon and 15 patients without malignancy. Only patients with body weight not exceeding 10% of the normal body weight, without history of diabetes mellitus and not treated with corticosteroids were classified for the study. Mean glycaemia and insulinemia values did not differ statistically in the investigated groups except statistically significantly higher serum insulin level in patients with cancer of the lung in the thirties minute of the test. Differences statistically significant were also not observed in retrospective analysis. However, an incidence of diabetes mellitus in patients with the cancer of the colon was 10.5% being higher than mean incidence of diabetes mellitus in this age group. Moreover, glucose load test has shown tolerance abnormalities in 4 patients with cancer of the colon, 1 patient with cancer of the lung, and 1 patient without malignancy. The obtained results indicate tendency to higher incidence of carbohydrate metabolism disorders in patients with cancer of the colon.     

Changes in plasma inbulin related to the type of dietary carbohydrate in overweight hyperlipidemic male patients

Five patients with mild diabetes mellitus or angina pectoris were studied, each of whom consumed two sequential diets containing 40 to 50% carbohydrate. When 75% of the dietary carbohydrate was derived from food containing polysaccharides, the mean plasma insulin response to oral glucose was decreased relative to that seen following complementary diets providing carbohydrate mainly as simple sugars. Under both dietary conditions, glucose tolerance was improved compared to that seen prior to the study. These results suggest that with sugar restriction an improvement in the efficiency of the pancreatic beta-cell mechanism occurs. This effect may have been mediated by changes in the rate of secretion of pancreatic glucagon, or by an enteric secretogogue of insulin.     

Diabetes mellitus and the exocrine pancreas

Diabetes and carbohydrate intolerance can occur in pancreatitis. Although one-half of patients with acute pancreatitis will have some evidence of glucose intolerance during their acute illness, few will require insulin administration on either a short- or long-term basis. The diabetes seen in acute pancreatitis is likely due to a combination of factors, including alerted insulin secretion, increased glucagon release, and decreased glucose utilization by the liver and peripheral tissue. Chronic pancreatitis is often associated with diabetes mellitus, with the incidence as high as 70 percent when pancreatic calcification is present. These patients tend to be very sensitive to the effects of insulin and hypoglycemia. This is probably secondary to concurrent hepatic disease, malnutrition, and a relative decrease in glucagon reserves. The diabetes seen in chronic pancreatitis is associated with decreased insulin production. Finally, although the endocrine pancreas may influence the exocrine gland through a portal system, primary diabetes mellitus probably does not result in clinically significant alterations in pancreatic exocrine function.     

The glucose tolerance, insulin response and pancreatic exocrine function in patients after acute pancreatitis

In 25 patients having a history of acute pancreatitis (AP) in anamnesis one year ago and in 12 control subjects the insulin response to oral glucose was investigated and in some cases the exocrine function of pancreas was evaluated. The disturbances in glucose tolerance occurred in about 30% of the patients and were associated with impairment of insulin response and deterioration of exocrine pancreatic function. The double cortisone and glucose load did not influence the glucose tolerance in the patients. In persons investigated during AP and one year later only slight improvement of insulin response was noted. The results support the significance of follow-up studies of carbohydrate tolerance and insulin response in patients after AP for the evaluation of the diabetic risk in such cases.     

Toward improving postgraduate medical education.

Twenty-two patients receiving 5 per cent glucose solution intravenously during an acute illness were studied for evidence of hyperglycemia. Those in whom blood sugar rose above 100 mg per 100 ml (Folin-Wu) during intravenous therapy subsequently had impairment of carbohydrate tolerance as measured by oral glucose tolerance tests. The data collected suggested that blood sugar of 100 mg per 100 ml (Folin-Wu) or more developing in such a setting is a clue to the presence of diabetes mellitus.     

Prevalencia de alteraciones del metabolismo hidrocarbonado en una población infanto-juvenil con obesidad grave

IntroductionThere is currently a disproportionate increase in childhood and adolescent obesity worldwide, together with other disorders involving substantial cardiometabolic risk in adulthood, such as alterations in carbohydrate metabolism.ObjectiveTo establish the prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) after an oral glucose tolerance test, and the prevalence of type 2 diabetes mellitus (DM-2) in a pediatric population with severe obesity. Additionally, we aimed to assess clinical metabolic differences between prediabetic obese patients and obese subjects without prediabetes.Material and methodsA cross-sectional study was carried out in children and adolescents with severe obesity (>97th percentile). The variables studied were age, sex, height, weight, body mass index, waist circumference, fasting plasma glucose and oral glucose tolerance test, insulinemia, insulin resistance assessed by the homeostasis model assessment (HOMA) index, glycated hemoglobin (HbA_1c), triglycerides, high-density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressure.ResultsA total of 133 patients were included: 67 boys (50.4%) and 66 girls (49.6%), with a mean age of 12.17±3.27 years. Fourteen patients (10.52%) had prediabetes (10 IFG, 3 IGT, 1 IFG+IGT): 7 girls and 8 boys, with a mean age of 13.2±3.3 years. One patient had DM2 (0.75%). Patients with prediabetes had significantly higher concentrations of fasting glucose (98±10.76 vs 88.53±6.3 mg/d; p=0.001), insulinemia (35.38±14.22 vs 22.95±14.30 μU/ml; p=0.009) and HOMA index (8.10±3.24 vs 4.89±3.27; p=0.004) than patients without impaired carbohydrate metabolism. These patients also had higher values of HbA_1c, triglycerides, blood pressure and HDL concentrations, although differences were not statistically significant.ConclusionsThe prevalence of prediabetes (IFG/IGT) in children with severe obesity was high (10.52%). These patients should therefore be investigated to establish early diagnosis and appropriate treatment. Obese patients with prediabetes have significantly higher levels of insulin and insulin resistance than individuals without impaired carbohydrate metabolism.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

Occurrence of spontaneous diabetes mellitus in a cynomolgus monkey (Macaca fascicularis) and impaired glucose tolerance in its descendants

Spontaneous diabetes mellitus was diagnosed in a cynomolgus monkey. Clinical and pathological features, such as abnormal glucose tolerance, loss of insulin response, or degeneration of pancreatic beta-cells, resemble human noninsulin-dependent diabetes mellitus. Two descendants of the monkey have developed impaired glucose tolerance and insulin response. Genetic factors seem involved in the appearance of carbohydrate intolerance in this family group of monkeys.     

Used of oral antidiabetic agents in pediatric patients - own observations

Our present investigation demonstrates that in adolescents with various impaired glucose homeostasis oral antidiabetic agents can be used to improve glucose metabolism. Metformin is widely used in pediatric patients and is considered to be the most effective oral agent. Metformin is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels. Addition of metformin to insulin in pediatric patients with type 1 diabetes mellitus improves metabolic control. Metformin acts by promoting glucose utilization and reducing hepatic glucose production. In many patients with type 2 diabetes, hyperglycemia can be reduced with appropriate changes in diet and exercise, however, some patients with type 2 diabetes and insulin resistance syndromes need pharmacological therapy to improve their metabolic control. The first oral agent concerned to use should be metformin. More severe pancreatic b-cell dysfunction in the group of children requires insulin therapy. Some forms of monogenic diabetes can be successfully managed by sulphonylurea agents. Metformin should be considered a first-line agent in girls with PCOS.     

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes.     

Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance. The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection.     

Two birds with one stone: novel glucokinase activator stimulates glucose-induced pancreatic insulin secretion and augments hepatic glucose metabolism

The hormones glucagon and insulin delicately regulate the concentration of blood glucose. When patients become resistant to the effects of insulin or produce too little of it to properly regulate glucose concentrations, then diabetes can result. Unfortunately, not all patients with insulin-resistant, type 2 diabetes mellitus respond to drugs that improve insulin sensitivity. However, there is reason to be hopeful. A new molecule that targets glucokinase (GK), the enzyme responsible for phosphorylating glucose in pancreatic beta cells and hepatic cells, acts to significantly reduce blood glucose concentrations in rodents. The GK activator RO-28-1675 increased the glucose affinity and Vmax of GK, and rats treated with RO-28-1675 had improved glucose tolerance and elevated glucose uptake in liver. These results provide the basis for improved drug design that may alleviate diabetes mellitus and the disorders that accompany it in patients.     

Hormonal responses to intravenous glucose and arginine in patients with pancreatitis

19 subjects with an acute episode of pancreatitis, and 5 patients with chronic pancreatitis received intravenous glucose tolerance tests with measurement of glucose, insulin and glucagon. Patients recovering from acute pancreatitis demonstrated defects in their ability to dispose of a glucose load. 10 patients had overt glucose intolerance; of these, 4 were insulin-deficient, 3 had a loss of an acute insulin response to glucose, and 3 had marked hyperglucagonemia with normal to increased insulin levels. These abnormalities were seen in response both to intravenous glucose and intravenous arginine. Therefore, according to this study, at least three factors are clearly implicated in the production of glucose intolerance after an acute episode of pancreatitis: hypoinsulinemia, delayed insulin secretory response and hyperglucagonemia.     

Chromium metabolism and its role in disease processes in man

Chromium is an essential element required for normal carbohydrate and lipid metabolism. Insufficient dietary Cr has been linked to maturity-onset diabetes and cardiovascular diseases. The dietary Cr intake of most individuals is considerably less than the suggested safe and adequate intake. Consumption of refined foods, including simple sugars, exacerbates the problem of insufficient dietary Cr since these foods are not only low in dietary Cr but also enhance additional Cr losses. Chromium losses are also increased due to pregnancy, strenuous exercise, infection, physical trauma and other forms of stress. Supplementation of Cr to normal free-living individuals often leads to significant improvements in glucose tolerance, serum lipids including high-density lipoprotein cholesterol, insulin and insulin binding. Chromium also tends to normalize blood sugar. Chromium supplementation of subjects with elevated blood sugar following a glucose load leads to a decrease in blood sugar while hypoglycemics respond to supplemental Cr by an increase in hypoglycemic glucose values, increased insulin binding and alleviation of hypoglycemic symptoms. In summary, dietary intake of Cr is suboptimal and this is exacerbated by increased Cr losses due to stress and certain refined foods including simple sugars that enhance Cr losses. Supplemental Cr is associated with improvements of risk factors associated with maturity-onset diabetes and cardiovascular diseases.     

Beta-cell dysfunctions and insulin resistance in subjects with increased risk for type 2 diabetes mellitus

The aim of this study was to test if a beta-cell defect is associated to deterioration of glucose tolerance early during the natural history of the type 2 diabetes mellitus . In 41 overweight women, with macrosomic infants in their antecedent deliveries, measures of insulin response and insulin sensitivity were derived from a short (45 min) iv glucose test. The early (EIR) and the late (LIR) phase insulin responses and the insulin sensitivity index (Si) were calculated. According the response to 75 g oral glucose test the subjects were divided into two groups: Imparired glucose tolerance (IGT;n = 12), and normal glucose tolerance (NGT; n = 29). EIR was reduced in IGT group (14.9 ± 3.6 vs 37.0 ± 4.0; p< 0.002). Glucose tolerance during oral glucose tolerance test (OGTT), correlated inversly to EIR (r=-0.45; n=41; p< 0.01). A strong correlation of EIR to LIR (r=0.88; n = 41; p< 0.001) but no correlation between glucose tolerance and Si was found.     

Inhibitory effect of PGE1 on the liberation of insulin induced by glibenclamide

Glycemia and insulinemia in rat blood samples have been determined at different times before and after administration of glibenclamide, PGE1, glibenclamide and PGE1, glibenclamide and glucose, PGE1 and glucose, and glibenclamide, PGE1 and glucose. PGE1 led to a partial inhibition of glibenclamide induced insulin release, with and without glucose administration, but a total inhibition did not occur. The inhibitory action of PGE1 on insulin secretion was also reflected on the glycemia curves. Defects in insulin release in diabetes could be due in part to an excessive production of PGs, that involve a failure in the beta-cells to respond to glucose signals. The present paper shows that glibenclamide secretory action was not cancelled out by PGE1. These results could explain the availability of glibenclamide in the treatment of diabetes mellitus.     

Metabolic abnormalities in first-degree relatives of type 2 diabetics

Diabetic relatives and obese subjects are at increased risk for development of diabetes mellitus, and therefore are classed as potential abnormality of glucose tolerance (POT-AGT). Disturbances of lipid and purine metabolisms have been reported in diabetic and obese non-diabetic subjects. In obese subjects above alterations are probably due to hyperinsulinemia. This study aimed at verifying whether similar metabolic abnormalities could be found in relatives of non-insulin dependent diabetic patients and whether they could be related to possible glucose intolerance. We have studied 10706 outpatients and 95 hospitalized subjects, aged between 20 and 50 years. We have selected 4 groups according to diabetic relationship and body mass index: A (normal weight subjects), B (obese subjects), C (normal weight NIDDM-relatives), D (overweight NIDDM-relatives). The NIDDM-relatives showed higher prevalence of hyperglycemia, as expected; furthermore the relatives with normal glucose tolerance had higher glucose area during OGTT. Serum levels of uric acid and insulin response to oral glucose were increased in all obese subjects, but abnormalities of lipid metabolism and fasting hyperinsulinemia were found only in obese NIDDM-relatives. These results suggest that family history of diabetes mellitus can be a risk for metabolic disturbance even in absence of glucose intolerance. Furthermore some metabolic disorders observed in obese subjects could be due to an associated and not sufficiently investigated family history of diabetes.     

Genetic susceptibility to non-insulin dependent diabetes mellitus and glucose intolerance are located in HLA region.

OBJECTIVES--To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes. DESIGN--Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance. SETTING--Two communities in Finland. SUBJECTS--Representative cohort of Finnish men aged 70-89, comprising 98 men with non-insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years. MAIN OUTCOME MEASURES--Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration. RESULTS--Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p < 0.0001)). CONCLUSIONS--These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.     

Control of postprandial hyperglycaemia by galactosyl maltobionolactone and its novel anti-amylase effect in mice

The ability to control carbohydrate digestion is useful in the treatment of diabetes mellitus and obesity. In the present study, we examined whether recently developed 4(2)-O-beta-D-galactosyl maltobionolactone (LG2O) having anti-amylase activity is able to control postprandial blood glucose concentration in mice. In addition, we tried to determine how LG2O regulates carbohydrate delivery in the gut lumen by conducting in vivo and in vitro studies. Male non-diabetic ddY mice and KK-A(y) mice, a spontaneously diabetic strain, had free access to a carbohydrate rich diet supplemented with LG2O (3 or 10 g/kg) for 0.5 hr, and blood glucose concentration was measured. LG2O suppressed any steep increase in postprandial blood glucose concentration in both ddY and KK-A(y) mice. Corresponding to the blood glucose response, LG2O also markedly suppressed any increase in postprandial plasma insulin concentration. After ingestion of the diet, LG2O produced a 1.5-3.5 fold increase in the gut contents and reducible sugar content in the small intestine but not in the stomach. Although alpha-amylase activity in the stomach was much lower compared with the activity in the small intestine, LG2O still strongly inhibited alpha-amylase activity in the stomach. In contrast, LG2O had little or no influence on alpha-amylase activity in the proximal intestine. From the in vitro carbohydrate digestion stimulation, LG2O at 7.5 mM decreased glucose production by 75% for dextrin, 25% for alpha-starch and 60% for raw starch. In conclusion, administration of LG2O inhibits carbohydrate digestion in the gut, and produces significant improvements in both blood glucose and insulin response following ingestion as part of the diet, and this evidence provides support for its therapeutic potential in treating diabetes mellitus and obesity.     

Prevalence of glucose intolerance in free-ranging Macaca fascicularis of Mauritius

Oral glucose tolerance tests (OGTTs) were carried out on 30 free-ranging long-tailed macaques (Macaca fascicularis) on the island of Mauritius, following the suggestion that severe glucose intolerance and diabetes mellitus might be prevalent in this macaque population. OGTTs revealed no evidence of frank diabetes mellitus in the sample. However, 13% of individuals showed impaired glucose tolerance, with preserved insulin secretion, suggesting the presence of the target tissue resistance to insulin characteristic of human noninsulin-dependent diabetes mellitus (NIDDM). The macaques with impaired glucose tolerance were neither obese nor aged. Glucose levels at all time points of the OGTT in normal macaques in our free-ranging sample were lower than reported in captive populations, perhaps due to greater physical activity. Our observations demonstrate that a genetic predisposition to glucose intolerance does exist in M. fascicularis, and that this condition, well documented in laboratory macaques, is not simply an artifact of captivity.