BACKGROUND: It has been hypothesized that fibrinogen clusters with several components of the metabolic syndrome, thus increasing its cardiovascular risk. The aims of the present study were to assess in a large population-based cohort of patients with type 2 diabetes (1) variables associated with fibrinogen and (2) the relationship between hyperfibrinogenemia, a number of components of the metabolic syndrome, and coronary heart disease (CHD). METHODS: We identified a cross-sectional, population-based cohort of 1574 patients with type 2 diabetes using multiple sources of ascertainment. Components of the metabolic syndrome were hypertension (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg and/or treatment with antihypertensive drugs), dyslipidemia (tryglicerides >2.82 mmol/l and/or HDL-cholesterol <1.03 mmol/l), hyperuricemia (uric acid >416 micromol/l) and increased albumin excretion rate (AER > or = 20 microg/min). RESULTS: Fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, even after adjustment for confounders. Prevalence of CHD increases linearly across quartiles of fibrinogen (from 26.1 to 40.6%, p=0.046). However, in logistic regression, after adjustment for both confounders and known risk factors for CHD, the role of fibrinogen is no more significant, whereas ORs for HbA(1c) between 6.8 and 8.8% and >8.8% vs values <6.8% are, respectively, 1.91 (95% CI 1.36-2.69) and 1.56 (1.07-2.27). CONCLUSIONS: This population-based study shows that fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, independent of major confounders. We also found that poor blood glucose control was associated with CHD.

Aged↗

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Labile and stable glycosylated hemoglobin during OGTT in healthy subjects and maturity-onset diabetics.

HbA1 levels were determined by a rapid chromatographic column test in 15 healthy subjects (HS) and in 15 maturity-onset diabetics (MOD), fasting and 2 h after glucose ingestion (100 g for HS, 50 g for MOD). Chromatography was carried out both before and after 6 h of red cell incubation in saline at 37 degrees C. HbA1 in HS at 0 and 120 min of OGTT was not significantly different, either before (6.24 +/- 0.61% and 6.22 +/- 0.62%) or after red cell incubation in saline (5.85 +/- 0.61% and 5.87 +/- 0.55%). Red cell incubation in saline significantly reduced HbA1 levels both at 0 and 120 min (2p less than 0.001). HbA1 in MOD before red cell incubation in saline, was slightly but significantly higher at 120 min (8.61 +/- 1.03%) than at 0 min (8.39 +/- 1.01%): 2p less than 0.001. After incubation in saline, this difference was cancelled (7.86 +/- 0.85% at 0 min and 7.97 +/- 0.83% at 120 min: n.s.). Post-incubation levels were lower than pre-incubation ones both at 0 and 120 min (2p less than 0.001). The HbA1 increment observed in MOD is significantly correlated (p less than 0.01; r=0.64) to the blood glucose increment observed at the glycemic peak. We conclude that hemoglobin glycosylation may show rapid changes also in MOD, reflecting blood glucose changes, whereas in HS the physiological glycemic excursions are not wide enough to produce rapid HbA1 changes. Since labile and stable HbA1 co-elute in the rapid chromatographic methods, red cell incubation in saline for 6 h at 37 degrees C is recommended as a simple procedure which allows the measurement of the stable fraction alone, i.e. the real index of long-term glycemic control, independent of rapid glycemic fluctuations.

Adult↗

PubMedDate not supplied

Diurnal variations in insulin secretion and insulin sensitivity in aged subjects.

Glucose tolerance tends to decrease in healthy aged subjects without family history of diabetes. Either reduced insulin secretion or insulin resistance may be responsible. Insulin secretion and insulin sensitivity were studied in 7 aged subjects (68-75 years) and 8 young controls (21-27 years). A 1-mg i.v. glucagon and a 5-U/m2 body area i.v. insulin test were run in each subject at 07(00) and at 19(00) on two different days to detect diurnal variations. An arginine test was also performed to evaluate pancreatic glucagon behavior. In the evening, young subjects presented a glucose tolerance impairment with significantly decreased plasma insulin levels, and a reduced hypoglycemic effect of exogenous insulin. Resistance to both endogenous and exogenous insulin in the aged was observed in the morning without significant morning/evening variations. Since the response to contra-insular hormones (GH in the insulin test, glucagon in the arginine test) was the same in both age groups, their role in the phenomenon could be ruled out. It is suggested that in the aged a stable reduction in number and/or a change in affinity of insulin receptors may occur. In addition, since aging is seen to be associated with the disappearance of diurnal variations in glucose tolerance and insulin secretion and sensitivity, and since a reduction in the receptor level of young healthy subjects in the evening has been reported by some authors, it is suggested that aged subjects may be less able to modulate the binding of insulin to its peripheral receptors in the course of the day.

Adult↗

PubMedDate not supplied

The treatment of unstable type I diabetes: conventional versus portable pump insulin administration.

The treatment of unstable insulin-dependent diabetics (UIDD) is still an unsolved problem. A comparison was made between optimized conventional treatment (OCT) (Ultralente + Actrapid at breakfast, Actrapid at lunch and Actrapid at dinner) and continuous s.c. insulin infusion (CSII) for 30 days in 10 UIDD outpatients. Continuous 24-h blood glucose monitoring with an artificial pancreas, fasting values of HbA1, plasma lipids, growth hormone, glucagon, daily urinary glucose and protein excretion were recorded after each treatment; a daily blood glucose profile was determined every week. Daily mean blood glucose values dropped significantly (p less than 0.01): from 187.2 +/- 66.6 (OCT) to 111.6 +/- 27.0 mg/dl (CSII), and hypoglycemic and ketotic events disappeared during CSII. A significant improvement (p less than 0.01 - p less than 0.001) in all other parameters was also observed. It is suggested that CSII may help to improve metabolic control and the quality of life in UIDD.

Adolescent↗

PubMedDate not supplied

Ganglioside treatment in diabetic peripheral neuropathy: a multicenter trial.

Ganglioside treatment was evaluated with a multicenter, randomized, double-blind, controlled, cross-over vs placebo trial in 140 insulin-treated diabetic subjects with peripheral neuropathy. The patients entered the study when they showed an impairment in at least two of the electroneurographic parameters, and were assigned to two protocols according to the presence and severity of their neurological symptoms. Ninety-seven diabetic subjects with no or mild symptoms were assigned to protocol I, whereas 43 symptomatic patients were assigned to protocol II. the treatment periods lasted 6 weeks with an intermediate washout period of 4 weeks. The treatment consisted in the daily i.m. administration of 20 mg gangliosides or of placebo. Electroneurographic parameters were recorded at the beginning and at the end of each treatment period, whereas clinical and metabolic data (mean daily plasma glucose, glycosuria and glycosylated hemoglobin) were evaluated every three weeks in protocol I and every two weeks in protocol II. No change in the metabolic parameters was observed throughout the trial period. However, the treatment induced a statistically significant improvement of paresthesias (protocol II) and of some electrophysiological parameters; in particular, ganglioside treatment improved MCV of peroneal nerve (p less than 0.03) in patients of protocol I, MCV o ulnar nerve (p less than 0.002) and SCV of median nerve (p less than 0.06) in patients of protocol II. Furthermore, 22 subjects of protocol II showed a 'drug preference' while 10 preferred placebo and 9 had no preference. In conclusion, ganglioside treatment seems to have a positive effect on diabetic peripheral neuropathy, improving both some symptoms and some electrophysiological parameters.

Adolescent↗

PubMedDate not supplied

Beta-blockers in hypertensive non-insulin-dependent diabetics: comparison between penbutolol and propranolol on metabolic control and response to insulin-induced hypoglycemia.

In a single blind randomized study the effects of a 4-week administration of propranolol (160 mg/day) and penbutolol (40 mg/day) on metabolic control and insulin-induced hypoglycemia were tested in 8 non-insulin-dependent diabetics with diastolic blood pressure between 95 and 110 mmHg. The recovery from hypoglycemia was not delayed by either drug; hypoglycemic nadir and Conard's K did not change significantly. Symptoms of hypoglycemia were inhibited to a lesser extent and pulse rate decrease was lower after penbutolol vs baseline (65 +/- 2.4 vs 77 +/- 2.4 beats/min, p less than 0.01) than after propranolol vs baseline (61 +/- 1.06 vs 77 +/- 2.4 beats/min p less than 0.001). Both drugs produced similar and significant effects on blood pressure both systolic and diastolic. There were no significant effects on fasting plasma glucose concentration, HbA1c, IRI, urinary C-peptide, triglycerides, total and HDL cholesterol and FFA. IRG decreased after penbutolol vs baseline 60 min after insulin injection (170 +/- 30.8 vs 125 +/- 15.4 pmol/l, p less than 0.05). These results indicate that the use of beta-blockers, in particular penbutolol, for mild to moderate hypertension may be considered the treatment of choice also in non-insulin-dependent diabetics at the therapeutic doses employed.

Blood Glucose↗

PubMedDate not supplied

Insulin receptors in adipocytes of non-diabetic and diabetic subjects. Preliminary report.

We have measured insulin binding to human adipocytes isolated from subcutaneous adipose tissue removed during surgery in normal and insulin-independent diabetics. Collagenase digestion, 125I-monoiodoinsulin and Scatchard's plot were employed to analyze the results. Different kinetic patterns emerged together with differences in the dissociation constant and receptor numbers: in normal subjects K1 was 4 X 10(-9) moles/1 and K20.5 X 10(-8) moles/1, and in diabetic subjects K1 was 2.24 X 10(-9) moles/1 and K2 0.52 X 10 10(-8) moles/1; the two classes of receptors were 100,000 and 300,000 per cell in normals and 50,000 and 180,000 in diabetics. It was clear that even slight diabetes leads to receptor deficiency in adipocytes, though it could not be determined whether this a primary, perhaps genetic, defect or secondary to antibody damage, as suggested by some workers. Feed-back between circulating insulin and specific receptor availability in cells is another possibility.

Adipose Tissue↗

PubMedDate not supplied

Effect of a somatostatin analog on insulin requirement and hormone levels in 6 insulin-dependent juvenile-onset diabetics subjected to artificial pancreas.

This study was performed in order to investigate the effect of a 12-h infusion of the somatostatin selective analog D-Trp8, D-Cys14 Serono, (SRIF-A), on insuli requirement and C-peptide (CP), growth hormone (GH) and glucagon (IRG) levels in 6 insulin-dependent diabetics submitted to 60-h artificial pancreas (Biostator Miles) metabolic control from 2000 of the first day to 0800 of the fourth day. Meals were given at 1200 and 1700 of the second and third day. Before meals and 1-2 h after meals, plasma levels of CP, GH and IRG were measured. The two 12-h periods (midday-midnight) with and without continuous SRIF-A 12-h infusion (40 microgram/h) were considered. The SRIF-A infusion caused a 20% reduction in insulin requirement (p < 0.05) and a slight but significant reduction of GH levels (p < 0.05). CP and IRG were unaffected.

Adult↗

PubMedDate not supplied

Metabolic and hormonal changes during exercise in healthy, diabetic and obese subjects.

The metabolic and hormonal changes during a standard physical exercise were studied in healthy subjects and in insulin-dependent diabetics well matched for body weight, and therefore submitted to a similar work load in a physiologic range, and in obese subjects that, owing to their weight, faced a significant heavier work in the same environmental conditions. Moderate work load did not lead to significant changes in metabolic and hormonal blood parameters (blood glucose, FFA and glycerol; insulin, glucagon, growth hormone and cortisol) in healthy subjects. A similar substrate homeostatis was seen in insulin-dependent diabetics, that however showed marked hormonal alterations. In these subjects, indeed, higher levels of plasma glucagon and GH were reached during work and in the recovery phase. Obese subjects, submitted to a heavier work load, presented a marked increase in blood glucose and glycerol which agrees with high GH and cortisol levels, and a subsequent increment of IRI which corresponds to a normalization of blood glucose and glycerol. Obese subjects, therefore, show a normal sensitivity to work load. Considerations about the work load in everyday life are discussed.

Adult↗

PubMedDate not supplied

Dietary guar gum supplementation does not modify insulin resistance in gross obesity.

Obesity is considered an insulin resistant state. Dietary guar gum supplementation is able to reduce blood glucose and plasma insulin response to a carbohydrate meal. In order to evaluate whether guar is able to reduce hyperinsulinemia and insulin resistance in gross obesity, we studied 9 obese patients, greater than 50% overweight with impaired glucose tolerance before and after 4 + 4 g/day guar for 6 weeks. Six patients repeated the treatment with 8 + 8 g/day guar after a 3-month interval. Guar was added to the usual diet in order to maintain the body weight constant. Pre-treatment and post treatment study included: total specific insulin binding on circulating monocytes; 3H-glucose infusion and euglycemic hyperinsulinemic clamp at approximately 100 microU/ml. The differences between post-treatment and pre-treatment values were not significant for any of the parameters studied. Fasting glucose production was: 2.17 +/- 0.33 SEM (pretreatment) vs 2.18 +/- 0.18 (4 + 4 g/day) vs 2.28 +/- 0.14 (8 + 8 g/day) mg/kg/min; glucose utilization was: 3.52 +/- 0.43 vs 3.22 +/- 0.44 vs 3.49 +/- 0.63 mg/kg/min; total specific insulin binding was: 2.80 +/- 0.20 vs 2.75 +/- 0.25 vs 2.78 +/- 0.31%; body weight was: 101.4 +/- 5.4 vs 100.2 +/- 6.2 vs 100.5 +/- 7.0 kg. These results indicate that dietary guar gum supplementation per se is unable to reduce insulin resistance in gross obesity if overweight is maintained constant.

Adult↗

PubMedDate not supplied

Insulin secretion and insulin sensitivity defects are a common feature of mild, clinically homogeneous, recently diagnosed type II (non-insulin-dependent) diabetics.

Alteration in insulin secretion and reduced peripheral sensitivity to the hormone have been reported in type II diabetes. In this paper, a comparison is made of basal glucose production (3H-6 glucose), insulin secretion and insulin sensitivity in vivo (hyperglycemic clamp) and in vitro (binding to circulating monocytes) in 24 patients with recently diagnosed type II diabetes, matched for age and fasting glycemia and divided into non-obese (14 subjects) and moderately obese (10 subjects), and in 9 non-obese controls. The non-obese diabetics were slightly hyperinsulinemic during fasting (10.8 +/- 1.0 vs 4.8 +/- 0.8 microU/ml in controls, p less than 0.0005), with a significant reduction in early and late insulin secretion (14.0 +/- 1.5 vs 20.8 +/- 2.0 microU/ml, p less than 0.01 and 24.8 +/- 3.3 vs 34.7 +/- 2.14 microU/ml, p less than 0.025). The insulin sensitivity index MCR/I was significantly reduced (2.30 +/- 0.32 vs 4.14 +/- 0.40, p less than 0.005). Endogenous glucose production was significantly increased (107 +/- 10.2 vs 84 +/- 3.7 mg/m2 per min, p less than 0.025) and displayed a positive correlation with fasting glycemia (r = 0.51, p less than 0.05). Insulin binding to monocytes was significantly lower than in controls (2.36 +/- 0.22% vs 4.06 +/- 0.32%, p less than 0.0005). Moderately obese diabetics also were significantly hyperinsulinemic in the fasting state (18.1 +/- 2.8 microU/ml, p less than 0.0005 vs controls) but, typically, lacked the early secretory phase (20.6 +/- 3.6 microU/ml vs baseline, n.s.). A similar increase of hepatic glucose production (107 +/- 11.2 mg/m2 per min, p less than 0.025 vs controls, n.s. vs non-obese diabetics) and decrease of peripheral sensitivity to insulin (MCR/I = 1.78 +/- 0.31, p less than 0.0005 vs controls, n.s. vs non-obese diabetics) was found in moderately obese diabetics, as well as a significant reduction of insulin binding to insulated monocytes (2.62 +/- 0.4% p less than 0.01 vs controls, n.s. vs non-obese diabetics). These results confirm that common defects of both non-obese and moderately obese type II diabetics are: lack of early phase of glucose induced insulin secretion, increase in hepatic glucose production and decrease of peripheral insulin sensitivity together with reduction of insulin binding to circulating monocytes. The hypothesis of a unique defect as a cause of hyperglycemia in type II diabetes in early clinical phase is not borne out by the results of this study. Moderate obesity, even if able to reduce insulin sensitivity, seems to be less important in determining hyperglycemia.

Adult↗

PubMedDate not supplied

Efficacy of continuous subcutaneous insulin infusion in unstable diabetes secondary to chronic pancreatitis: a case report.

Explore the source record for details and available documents.

Blood Glucose↗

PubMedDate not supplied

To what extent does the artificial pancreas facilitate the surgery of preoperatively not localized insulinomas?

The patient study has been performed in order to evaluate the usefulness of the artificial pancreas in the surgical management of previously not localized insulinomas. In the 4 patients studied, blood glucose was maintained both overnight and during surgery up to a preselected individualized level in order to avoid hypoglycemia. During surgery, only one patient required dextrose infusion. The continuous intrasurgical monitoring of blood glucose in the 4 cases examined showed that: (1) anesthesia induction, surgical incision and viscera mobilization were accompanied by a rise in blood glucose (10.30 mg/dl), reaching the highest levels 30-40 min after the start of the operation; (2) adenoma manipulation was followed by a drop in blood glucose (10.40 mg/dl), reaching the lowest level after 30-40 min; (3) adenoma resection was followed by a rise in blood glucose (25-40 mg/dl), particularly evident after 30-40 min. It is concluded that the artificial pancreas is certainly useful during surgery of insulin-producing tumors, allowing continuous monitoring of glycemia and avoiding dangerous blood glucose excursions: however, when the insulinoma is not identified during surgery, the periods elapsing between the surgical phases and the blood glucose changes observed can be too prolonged to ensure successful conservative serial pancreatectomy in all cases.

Adenoma↗

PubMedDate not supplied

Urinary excretion of glycated albumin in insulin-dependent diabetic patients with normal urinary albumin excretion.

Glycation involves both circulating proteins, such as albumin, and structural proteins, such as the components of the glomerular basement membrane. A preferential excretion of glycated albumin (more anionic at physiological pH compared with unmodified plasma albumin) has been reported by some authors, but not by others. We therefore investigated the selectivity index (renal clearance of non-glycated albumin/clearance of glycated albumin) in 25 insulin-dependent diabetic patients with normal urinary albumin excretion and in 19 well-matched control subjects. The selectivity index was significantly higher in diabetic patients than in control subjects: 1.38 +/- 0.05 SEM vs 0.98 +/- 0.02, p less than 0.0001. This result is not consistent with a preferential urinary excretion of glycated albumin, at least in normoalbuminuric uncomplicated insulin-dependent diabetic patients.

Adult↗