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Serum ketone response to glucagon as a marker of insulin dependency in diabetics.

The serum ketone response to glucagon was measured in 10 patients with IDDM and 37 with NIDDM. In both groups, serum 3-hydroxybutyrate increased significantly after intravenous injection of 1 mg glucagon. The difference between the serum level of 3-hydroxybutyrate at 30 min and basal level [delta 3-OHBA(30')] was 133 +/- 25 mumol/l in the patients with IDDM, 13 +/- 8 mumol/l in those with NIDDM treated by diet alone or with oral hypoglycemic agents and 23 +/- 13 mumol/l in those with NIDDM treated with insulin. The delta 3-OHBA(30') was significantly greater in IDDM patients than in both groups of NIDDM patients (P less than 0.001). The delta 3-OHBA(30') was greater than 87 mumol/l in eighty percent of IDDM patients, but smaller than 87 mumol/l in both groups of NIDDM patients. The delta 3-OHBA(30') was correlated with the difference between the plasma level of C-peptide at 6 min and basal level [delta CPR(6')] (r = -0.540, P less than 0.001). The delta 3-OHBA(30') was not correlated with fasting plasma levels of glucose, fructosamine or hemoglobin A1c. These observations show that measurement of the serum ketone response to glucagon is a useful marker of insulin dependency. In order to determine insulin dependency, the simultaneous measurement of concentrations of ketones and C-peptide is indicated during the glucagon stimulation test.

3-Hydroxybutyric Acid↗

Comparisons of home blood glucose testing and glycated protein measurements.

We examined the relationships between 4 glycated protein assays and home blood glucose monitoring (HBGM) in 26 children with poorly-controlled insulin-dependent diabetes mellitus (IDDM) during a period of improved management. At 2 week intervals for 6 visits (12 weeks in total), HBGM records were collected and a blood sample was obtained for measurement of glycated proteins and glucose. Assays included glycated hemoglobin (GHb) and glycated serum proteins (GP) by boronate affinity chromatography, hemoglobin A1C by PolyCAT A high performance liquid chromatography (HAC) and fructosamine (FA). All 4 glycated protein levels declined significantly over the 12 week period. Significant correlations between the glycated proteins and HBGM were observed over 2 week intervals. None of the 4 assays were affected by the glucose level in the sample. Changes in mean HBGM readings over 2 week intervals were correlated with both FA and GP with wide prediction intervals. Over cumulative 2 week intervals, which may more accurately reflect longitudinal trends, all 4 glycated proteins were correlated with mean HBGM readings. At each cumulative interval, GHb and GP showed the largest variation with MBG, while FA showed the least variation with MBG. Our data indicate that of the 4 assays tested, FA has limited clinical values as compared to other glycated protein assays, whereas assays based on boronate affinity chromatography (GHb and GP) provide the most useful clinical indicators of short-term changes in glycemic control. The clinical utility of a new HPLC method for determination of glycated hemoglobins is also demonstrated.

Adolescent↗

Phosphate promotes glycation of antithrombin III which interferes with heparin binding.

Nonenzymatic glycation of antithrombin III has been reported to cause the reduction of heparin-catalyzed thrombin-inhibiting activity in diabetes. The effect of in vitro nonenzymatic glycation of pure antithrombin III on heparin binding and heparin-potentiated activity under a variety of buffers and pH values was studied to further clarify the physiological significance of this reaction. The extent of glycation, measured by the fructosamine assay and [14C]glucose binding, was enhanced by the presence of phosphate ion (pH 7.45, 8.5 and 9.5) and increased linearly with increasing phosphate ion concentration from 0.01 to 0.2 M phosphate. Conversely, the heparin-catalyzed antithrombin activity decreased from 93.1% of controls for 0.01 M phosphate to 73.5% for 0.2 M phosphate as the extent of glycation increased. The increase in intrinsic fluorescence induced by binding of heparin to antithrombin III was also moderated by glycation of antithrombin III in a dose-dependent manner with a negative correlation coefficient of -0.94. Direct measurement of the heparin binding by affinity chromatography showed a decrease in the heparin-binding fraction which correlated with the degree of glycation and the decrease in heparin-catalyzed activity. These studies suggest that nonenzymatic glycation may be responsible for the reduction in antithrombin III activity observed in some diabetics.

Antithrombin III↗

Age-related changes in the glycation of human aortic elastin.

Non-enzymatic glycation of proteins is a consequence of hyperglycemia in diabetes and correlates with aging. The aim of the study was to investigate age-related changes in the glycation of human aortic elastin in healthy subjects by two approaches: (1) assessment by fluorescence method of formed in vivo advanced glycation end products (AGEs) of elastins, purified from human aortas, obtained from different age groups; (2) in vitro glycation of elastins from different age groups and investigation of their capacity to form early (by colorimetric nitroblue tetrazolium method) and AGEs (fluorescence method). Human insoluble elastins were prepared from macro- and microscopic unaltered regions of thoracic aortas, obtained from 68 accident victims, distributed in 15 age-groups, using the method of Starcher and Galione. Soluble alpha-elastins were obtained by the method of Partridge et al. The direct assessment of Maillard reaction related fluorescence in the age groups showed increase of the fluorescence with age. The 'young' elastin had the highest capacity to form both fructosamine and AGEs under glycation in vitro. The glycation of 'old' elastin did not increase markedly during the incubation. These results are consistent with the interpretation that because of its long biological half-life, elastin is susceptible to the slow process of glycation and the following modifications would contribute to the age-related changes of connective tissue.

Adolescent↗

A comparison of the Glycosylation Gap and Hemoglobin Glycation Index in patients with diabetes.

PROBLEM: The Glycosylation Gap (GGAP) based on fructosamine (F) measurement and the Hemoglobin Glycation Index (HGI) based on mean blood glucose (MBG) are two indices of between-individual differences in glycated hemoglobin (HbA1c) adjusted for glycemia. We sought to simultaneously compare GGAP with HGI and other estimates of glycemia. METHODS: HbA1c, F, and MBG level were obtained at a clinic visit from 62 patients with Type 1 diabetes. GGAP and HGI were calculated from the data as previously described. The variables were compared by correlation analysis. The concordance of patient classification by GGAP and HGI was compared by weighted kappa test. RESULTS: The mean HbA1c=11.1+/-2.7%, F=372.0+/-136.6 mol/l, MBG=186.5+/-58.4 mg/dl, HGI=0.0+/-2.0, and GGAP=0.0+/-1.9. MBG, HbA1c, and F were all highly correlated with each other. The HGI and GGAP were highly correlated (r=.73, P<.0001) and similar in both magnitude and direction. There was good agreement between HGI and GGAP classifications of patients into high, moderate, and low glycation groups (P<.0075). CONCLUSIONS: GGAP and MBG give similar information regarding between-patient differences in HbA1c among patients with diabetes. Thus, biological variation in HbA1c is not an artifact of variability in glucose measurements comprising the MBG. Individual patient factors influence the intracellular glycation of HbA1c in addition to the effect of extracellular glycemia, which is manifested as a between-individual biological variation in HbA1c.

Blood Glucose↗

The Fasting Hyperglycaemia Study: I. Subject identification and recruitment for a non-insulin-dependent diabetes prevention trial.

Subjects at increased risk for developing non-insulin-dependent diabetes mellitus (NIDDM) were encouraged via a public awareness campaign, general practitioners, or a direct approach (in the case of women with previous gestational diabetes) to attend one of three English and two French centers for fasting plasma glucose (FPG) measurement. Of 1,580 subjects (mean +/- SD age, 47 +/- 10 years), 29% were male, 56% had a diabetic relative, 20% had a history of elevated blood glucose or glycosuria, and 9% previously had gestational diabetes. Thirty-one percent (493) had an initial increased fasting glucose ([IFG] 5.5 to 7.7 mmol.L-1), 3% (41) a diabetic fasting glucose ([DFG] > or = 7.8 mmol.L-1), and 66% (1,046) a normal fasting glucose ([NFG] < 5.5 mmol.L-1). Four hundred forty-one of the 493 returned for a second FPG measurement, and 67% (293) of these had a similar value on repeat testing 2 weeks later. A 75-g, 2-hour oral glucose tolerance test (OGTT) in 223 of these subjects showed that 37% (83) had impaired glucose tolerance (IGT), 26% (58) diabetes mellitus (DM), and 37% (82) normal glucose tolerance (NGT). Seven percent of self-referred patients had NIDDM by World Health Organization (WHO) criteria. Eighty-eight percent of those with an initial DFG had an increased glycated hemoglobin (> 6.2%), and 75% an increased fructosamine (> 282 mumol.L-1). While these two glycemic measures provided good discrimination for diabetes, neither were reliable in detecting those with increased but not diabetic FPG values. In conclusion, 293 (19%) of 1,580 self-referred subjects were identified as having persistently increased FPG, and 227 have been entered into a randomized NIDDM prevention trial evaluating healthy-living advice and sulfonylurea therapy.

Adult↗

Decreased activity of arachidonate 12-lipoxygenase in platelets of Japanese patients with non-insulin-dependent diabetes mellitus.

To study the metabolism of the platelet 12-lipoxygenase pathway in diabetes, we evaluated the correlation between the activity and amount of arachidonate 12-lipoxygenase in the platelets of patients with non-insulin-dependent-diabetes mellitus (NIDDM). There were four parts in this investigation: (1) examination of abnormalities in platelet 12-lipoxygenase in patients with NIDDM recruited from the Hospital of Juntendo University School of Medicine; (2) comparison of 12-lipoxygenase in the platelets of non-obese NIDDM patients without angiopathy versus normal subjects matched for age, sex, and body mass index (BMI); (3) evaluation of gender differences; and (4) assessment of the potential influence of glycemic control. The activity of 12-lipoxygenase was assayed by incubation of [1-14C]arachidonic acid with the platelet cytosol. The reaction mixture was extracted and separated by thin-layer chromatography, and the radioactive end products were detected. The activity of 12-lipoxygenase in the platelets of patients with NIDDM was significantly less than in normal subjects (P < .003), whereas the amount of 12-lipoxygenase protein did not differ between the two groups. Thus, the specific activity of 12-lipoxygenase in diabetic patients was significantly less than that of normal subjects (P < .001). The enzyme activity and the specific enzyme activity of 12-lipoxygenase in non-obese NIDDM patients without angiopathy were significantly lower than the values in normal subjects matched for gender, age, and BMI (P < .006 and P < .0007, respectively). No significant difference in the activity or amount of platelet 12-lipoxygenase was observed between males and females matched for age, BMI, and disease. In addition, no relationship was observed between 12-lipoxygenase activity and blood glucose levels measured at the time of specimen collection. However, slight negative correlations were noted between 12-lipoxygenase activity and 1,5-anhydroglucitol, hemoglobin A1c (HbA1c), and fructosamine (r = .369, -.354, and -.279, respectively). When recombinant 12-lipoxygenase was incubated with varying concentrations of glucose or fructose, enzyme inactivation was related to the length of incubation, and was unaffected by glucose or fructose. These observations suggest that the activity of 12-lipoxygenase in the platelets of patients with NIDDM is decreased by prolonged hyperglycemia. The mechanism involved requires further investigation.

Adult↗

Continuous glucose monitoring for the evaluation of gravid women with type 1 diabetes mellitus.

OBJECTIVE: To compare the daily glycemic profile reflected by continuous and intermittent blood glucose monitoring in pregnant women with type 1 diabetes and to compare the treatment protocols based on the two monitoring methods. METHODS: The study sample consisted of 34 gravid patients at gestational weeks 16-32, with type 1 diabetes being treated by multiple insulin injections. Data derived from the continuous glucose monitoring system for 72 hours were compared with finger stick glucose measurements performed 6-8 times per day. During the study period, patients documented the time of food intake, insulin injections, and hypoglycemic events. Data on demographics, gravidity, parity, body mass index, hemoglobin A1c, and fructosamine levels were collected for each patient. RESULTS: An average (+/- standard deviation) of 780 +/- 54 glucose measurements was recorded for each patient with continuous glucose monitoring. The mean total time of hyperglycemia (glucose level greater than 140 mg/dL) undetected by the finger stick method was 192 +/- 28 minutes per day. Nocturnal hypoglycemic events (glucose level less than 50 mg/dL) were recorded in 26 patients; in all cases, there was an interval of 1-4 hours before clinical manifestations appeared or the event was revealed by random blood glucose examination. Based on the additional information obtained by continuous monitoring, the insulin therapeutic regimen was adjusted in 24 patients (70%). CONCLUSION: Continuous glucose monitoring can diagnose high postprandial blood glucose levels and nocturnal hypoglycemic events that are unrecognized by intermittent blood glucose monitoring and may serve as a basis for determining treatment regimens. A large, prospective study on maternal and neonatal outcome is needed to evaluate the clinical implications of this new monitoring technique.

Adult↗

Gestational diabetes screening of a multiethnic, high-risk population using glycated proteins.

In populations with a high incidence of gestational diabetes (GDM), any form of oral glucose testing for screening or diagnosis excessively strains the health care system. We investigated the value of glycated proteins as potential screening tests in 430 pregnant women, i.e. protein corrected fructosamine (cFRUC) and hemoglobin A1c (HbA(1c)) both alone and in combination for a GDM diagnosis confirmed by the 'gold standard' 100-g oral glucose tolerance test (OGTT). Two cut-off values were used for each test, the upper to rule in and the lower to rule out GDM. At the lower cut-off values for cFRUC of 210 micromol/l and HbA(1c) of 5%, the sensitivities achieved were 92.2 and 92.1% while the negative predictive values were 88.9 and 86.9%, respectively. The upper cut-off values did not achieve acceptable positive predictive values to be useful for ruling in GDM. Screening of our multiethnic, high-risk pregnant population with a combination of cFRUC and HbA(1c) on a single fasting sample would have avoided the cumbersome OGTT (by ruling out GDM) in 37.9% women with only a 3.9% misclassification rate. This potentially simpler approach, though not universally applicable, would be clinically useful and more acceptable to patients in selected high-risk populations.

Adolescent↗

Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes.

The prandial glucose regulator repaglinide has a rapid onset of action, a short half-life and is metabolised mainly by the liver. Here we report the findings of a 10-week, double-blind, parallel, placebo controlled, randomised trial with repaglinide in 25 diet-treated, sulphonylurea-naïve patients with Type 2 diabetes. Repaglinide was titrated, based on capillary blood glucose, from 0.5 mg to a maximum of 4 mg, preprandially with breakfast and dinner. After 10 weeks, repaglinide was associated with a decrease in HbA(1c) of 2.3%Hb relative to the placebo group (P=0.018). This reflected a 30% decrease within the repaglinide group from a mean HbA(1c) of 7.0 to 4.9%Hb (P<0.002). Repaglinide was also associated with a decrease in fructosamine, by 0.88 mmol/l, relative to placebo (P<0.001), with a 20% decrease (from 3.80 to 3.04 mmol/l) within the repaglinide group (P<0.001). Fasting and postprandial blood glucose concentrations decreased in association with repaglinide by 3.6 and 6.4 mmol/l, respectively, relative to placebo (P<0.001 in each case). Within the repaglinide group fasting and postprandial blood glucose decreased by 3.9 and 6.2 mmol/l, respectively (P<0.001 in each case). The number of patients reporting hypoglycaemia in the repaglinide group was similar to placebo (15 vs. 20, respectively; NS). Test meal assessments confirmed that repaglinide effectively controls glucose levels by stimulating mealtime insulin secretion. Fasting serum insulin concentration was not raised compared to baseline or placebo during repaglinide therapy, albeit that fasting glucose levels were decreased by repaglinide. Twice-daily meal-related insulin secretagogue therapy with repaglinide, a new short and rapid-acting prandial glucose regulator, is capable of improving all measures of glycaemic control without increased hypoglycaemia or fasting hyperinsulinaemia.

Area Under Curve↗

Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting.

This study compared treatment with a prandial glucose regulator (repaglinide) and a sulphonylurea (glibenclamide) in Muslim Type 2 diabetic patients who practice Ramadan fasting. Two hundred and thirty-five patients, previously treated with a sulphonylurea, were randomised to receive either repaglinide (n=116, preprandially three-times daily) or glibenclamide (n=119, preprandially once- or twice-daily) 6 weeks before Ramadan. During Ramadan, patients changed their eating pattern to two meals daily, and the daily dose of repaglinide was redistributed to two preprandial doses. After Ramadan, patients resumed their regular meal pattern and treatment dosage for 4 weeks. During Ramadan, a statistically significant reduction in mean serum fructosamine concentration from baseline was observed in the repaglinide group (-16.9+/-4.9 micromol/l, -3.8%, P<0.05) but not the glibenclamide group (-6.9+/-4.8 micromol/l, -0.8%). Difference in change in HbA(1c) from baseline was not statistically significant between groups. The number of hypoglycaemic events with midday blood glucose <4.5 mmol/l was significantly lower in the repaglinide group (2.8%) than the glibenclamide group (7.9%) (P=0.001). Apart from hypoglycaemia, both treatments were equally well tolerated. Type 2 diabetic Muslims using prandial repaglinide showed a trend towards better glycaemic control and had a lower frequency of hypoglycaemia than patients using glibenclamide during Ramadan.

Biomarkers↗

No difference in serum sialic acid in type 2 diabetic patients from the United Arab Emirates with and without diabetic retinopathy.

Serum total sialic acid (TSA) has recently been shown to be related to diabetic retinopathy. However, there is some controversy as this may be true in European Type 2 diabetic patients but not South Asians. There are few data looking at serum TSA expression in Arab Type 2 diabetic patients from the United Arab Emirates (UAE) and we wished to test the hypothesis that there may be different serum TSA expression in Arab Type 2 diabetic patients as regard to retinopathy. Sixty-five Type 2 diabetic patients from the UAE were studied (19 male and 46 female, age 57.5+/-9.8 (45-74) years, duration of diabetes 9.4+/-5.7 (0-22) years. The serum TSA in 13 patients with diabetic retinopathy was 757+/-130 mg/l and 782+/-163 mg/l in those without retinopathy (NS). There was no significant correlation between serum TSA and patient age, serum fructosamine, diabetes duration, or blood pressure. As in South Asians serum TSA does not appear to be elevated in Type 2 diabetic patients from the United Arab Emirates with diabetic retinopathy.

Aged↗

Transjugular intrahepatic portosystemic shunt (TIPS) augments hyperinsulinemia in patients with cirrhosis.

BACKGROUND/AIMS: Cirrhosis of the liver is characterized by glucose intolerance and hyperinsulinemia. Both increased insulin secretion and decreased insulin clearance appear to contribute to hyperinsulinemia in cirrhotic patients. A decrease in hepatic insulin extraction rate may be due either to hepatocellular dysfunction or to portosystemic shunting with decreased first-pass insulin clearance. METHODS: To specifically address the contribution of portosystemic shunting to the pathogenesis of hyperinsulinemia in cirrhotic patients, we analyzed glycemic control and insulin levels in fasting serum in 23 cirrhotic patients before and after transjugular intrahepatic portosystemic shunt (TIPS). RESULTS: Compared to respective values in healthy controls, C-peptide, insulin and proinsulin concentrations at baseline were increased by 340%, 120% and by 100% in cirrhotic patients (all p<0.05). In cirrhotic patients insulin levels before TIPS averaged 104+/-73 pmol/l and increased by more than 50% to 163+/-118 pmol/l after TIPS (p<0.01), whereas levels of C-peptide and proinsulin showed no significant change. Glucose and fructosamin levels also remained unchanged after TIPS. CONCLUSION: Our data demonstrate that TIPS does not impair glycemic control in cirrhotic patients and that an increase in portosystemic shunting augments hyperinsulinemia, most likely by decreasing hepatic insulin clearance.

Ascites↗

Serum alpha-1-antitrypsin concentration during normal and diabetic pregnancy.

OBJECTIVES: The aim of this study was a comparison of serum alpha-1-antitrypsin (AAT) concentration in the course of normal and diabetic pregnancy. METHODS: Serum AAT concentration was determined on NOR-Partigen plates (Behring Diagnostics GmbH, Marburg). The studied material included healthy women without pregnancy (n=14), healthy pregnant women in the first trimester (n=12), second trimester (n=15), third trimester (n=15), and 16 pregnant women with type-1 diabetes mellitus studied prospectively in successive stages of pregnancy. RESULTS: In the first trimester of normal pregnancy, a significant increase of serum AAT concentration was observed in comparison with healthy women without pregnancy (P<0.01). In all stages of pregnancy with type-1 diabetes mellitus, a higher increase of AAT concentration was found as compared with healthy pregnant women (P<0.0001), especially in third trimester. There was no correlation shown between concentration of AAT and fructosamine in the serum of healthy and diabetic pregnant women (P>0.05). CONCLUSIONS: During normal and diabetic pregnancy, an increase of serum AAT concentration occurred with the regression lines exhibiting a different slopes. The highest AAT concentration was observed in third trimester of diabetic pregnancy. Increase in concentration of AAT in the serum of pregnant women with diabetes does not depend on the value of glycaemic control.

Adult↗

Clinical value of detecting microalbuminuria as a risk factor for pregnancy-induced hypertension in insulin-treated diabetic pregnancies.

OBJECTIVE: We evaluated the role of clinical non-overt stage III diabetic nephropathy concerning the development of more frequent hypertensive complications during pregnancies of women requiring insulin. METHODS: 122 unselected pregnant women treated with insulin were enrolled in the study, of whom 56 were type-1 diabetic patients and 66 patients had gestational diabetes. In 24-h urine samples, excretion rates of albumin (UAE) and beta(2)-microglobulin were determined by nephelometric analysis and a radioimmunoassay, respectively. These parameters were also measured in the serum as well as HbA(1c), fructosamine and daily blood glucose profiles. RESULTS: Sixteen (15.7%) women had an elevated UAE (>30 mg/24 h), of whom three had macroalbuminuria (UAE>300 mg/24 h). Thirteen (12.7%) insulin-treated women showed microalbuminuria during pregnancy, eight with type-1 diabetes and five with gestational diabetes requiring insulin. In the entire group hypertension was observed in seven (6.9%) women of whom six had microalbuminuria. The sensitivity and specificity were 85.7% and 92.6%, respectively. The positive predictive value reached 46.2%, whereas the negative predictive value was 98.9%. CONCLUSION: Measurement of UAE in diabetic pregnancies seems to be an useful additional parameter for risk evaluation of hypertensive disorders.

Adolescent↗

The pathogenic effects of experimental cyathostome infections in ponies.

Nine pony breed foals were reared indoors, then allocated to one of three groups infected with either 3.9 million (Group A) or 3.15 million (Group B) cold-conditioned third stage cyathostome larvae or kept as uninfected controls (Group C). The larvae were administered as a 'trickle' infection of 150000 larvae per dose, three times weekly. Blood biochemical and haematological analyses were performed weekly and faecal worm egg counts bi-weekly. Complete parasitological examinations were performed on all ponies at various times post-initial infection (PI): one infected animal at 9 weeks PI, four animals (three infected, one control) at 20 weeks PI and four animals (two infected, two controls) at 60-62 weeks PI. All ponies in the infected groups experienced a marked reduction in weight gain and two animals developed clinical disease: one pony developed intermittent diarrhoea and colic 8 weeks PI; another pony developed intermittent diarrhoea between 30 and 52 weeks PI. All infected ponies had decreased serum fructosamine concentrations and five had decreased serum albumin, which were first apparent 4-6 weeks PI. Alterations in the composition of serum globulins were detected in all ponies. Transient neutrophilia was observed in five animals from the infected groups 3-9 weeks PI. Serum alkaline phosphatase concentrations were increased in one pony between 30 and 60 weeks PI. During the course of the experiment, faecal samples from all infected animals were negative for worm eggs. At necropsy, cyathostome larvae were present within the mucosa of the large intestine of all infected ponies, however the mucosal larval counts varied considerably between individuals.

Alkaline Phosphatase↗

Retinol and alpha-tocopherol in serum of type 1 diabetic patients with intensive insulin therapy: a long term follow-up study.

OBJECTIVE: We evaluated the effect of intensive insulin therapy and glycemic control in patients with type 1 diabetes on biochemical markers of vitamin A and E. METHODS: Fifty-seven patients with type 1 diabetes were enrolled in a follow-up study for 3 to 33 mo. At entrance, all patients were on conventional insulin therapy or recently had been diagnosed with the disease. Intensive insulin therapy (multiple daily glycemia records and at least three insulin doses daily) was established, and every 3 to 6 mo patients were screened for clinical, biochemical, and hematologic indexes. Biochemical markers of vitamin A and E nutrition status were measured at each visit by a quality-controlled high-performance liquid chromatography. RESULTS: At entrance, serum retinol concentrations, but not the ratio of alpha-tocopherol to cholesterol, showed a negative correlation with increasing values of HbA1c and insulin dose, neither of which was significant in multiple regression models. With intensive insulin therapy, a trend to normalize parameters of glycemic control (HbA1c and fructosamine) was observed within subjects and on a group level. However, no significant changes were observed in serum retinol or alpha-tocopherol:cholesterol ratio according to the metabolic control of the disease. CONCLUSIONS: Patients with type 1 diabetes under intensive insulin therapy tend to normalize the clinical parameters of glycemic control, although this improvement does not significantly affect biochemical markers of vitamin A and E status.

Adolescent↗

Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia.

Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested.

Aged↗