Insulin-dependent Diabetic Subjects Research Articles

114-OR: T1DM in the Chronically Undernourished: Rural Ethiopia

T1DM results from the interaction of genetic and environmental factors; the classical phenotype has been based largely on people of European background. However, Africa is a continent of enormous genetic diversity and extreme environmental conditions; do these differences have an impact on the T1DM phenotype? A consecutive series of recently diagnosed insulin-dependent diabetic subjects (n=236, ≤35 years) and controls (n=200), were recruited from the ethnic Amhara of rural NW Ethiopia. We assessed their demographic and socio-economic characteristics, measured non-fasting C-peptide, diabetes-associated autoantibodies, and HLA-DRB1 alleles. With genome-wide genotyping we performed principal component analysis (PCA) and a genome-wide association study (GWAS), and calculated a T1DM genetic risk scores (GRS) to compare their genetic background with known European T1DM determinants. Patients presented with low BMI, stunted growth, and were insulin sensitive; only 15.3% had diabetes onset ≤15 years. C-peptide levels were low but not absent (P=0.03). With clinical diabetes onset at ≤15, 16-25, and 26-35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had GADA as a single antibody; the prevalence of IA-2A and ZnT8A was low in all age groups. PCA showed that the Amhara genomes falls between those of ancestral European and ancestral African genomes. HLA-DRB1*03:01 and HLA-DRB1*04 were positively associated with diabetes while HLA-DRB1*15 was protective (P<0.0008 for each). The mean T1DM GRS (derived from European data) was higher in patients than controls (P=1.50x10-6). Autoantibody positive patients showed suggestive GWAS significance (P<5x10-6) with SNPs in the MHC region known to explain half of the T1DM heritability in Europeans. Thus, insulin-dependent diabetes in rural Ethiopia does have the immunogenetic characteristics of T1DM. The phenotypic differences between T1DM in rural Ethiopia and the industrialized world could be due, at least in part, to chronic undernourishment. Disclosure E.R. Trimble: None. S.A. Balcha: None. A.G. Demisse: None. D.L. Cousminer: None. R. Mishra: Employee; Self; GlaxoSmithKline plc. B.F. Voight: None. K. Lorenz: None. T. Vartak: None. S.T. Jerram: None. K.M. Hodge: None. S. Schwartz: Advisory Panel; Self; Intarcia Therapeutics, Janssen Pharmaceuticals, Inc. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Salix Pharmaceuticals. A. Holmes: None. A. Gamper: Stock/Shareholder; Self; GlaxoSmithKline plc., Unilever. H.F. Wilson: None. A.J. Williams: None. R.D. Leslie: None. S.F. Grant: None. D.I.W. Phillips: None. Funding American Diabetes Association (1-17-PDF-077 to D.L.C.); Association of Physicians of Great Britain and Ireland; National Institutes of Health (1K99HD099330-01, R01DK085212); Diabetes UK

Comparative study of sperm motility in Metformin-using and Insulin-dependent diabetics

Background: Diabetes mellitus (DM) represents one of the greatest threats to modern global health. DM may affect male reproductive function at multiple levels as a result of its effects on spermatogenesis, sperm motility, sperm morphology, and change in sperm structure.
 Methods: The present study deals with sperm motility and sperm morphological changes associated with diabetes in the male population. In this study, 50 insulin-dependent and 50 metformin users were selected, with ages of males ranging from 26-54 years and duration of diabetes distributed over 3-15 years. Both insulin-dependent and metformin-using diabetic subjects were evaluated for sperm analysis.
 Results: Sperm analysis data showed a significant increase (p ±0.0005) in total sperm count in insulin-dependent diabetic men. However, sperm motility was found to be about 10-15% less in insulin-dependent patients compared to metformin users. Moreover, sperm morphology was improved in 6% of metformin users compared to insulin-dependent diabetics.
 Conclusion: Our study concludes that metformin does not significantly affect sperm count. However, it does significantly affect sperm motility, when compared to insulin-dependent diabetic men. This study established an important relationship between diabetes and sperm motility, which reflects the reproductive capabilities of men.

Haemorheological changes in response to insulin-induced hypoglycaemia in young insulin-dependent diabetic patients and healthy control subjects

Haemorheological changes in response to insulin-induced hypoglycaemia in young insulin-dependent diabetic patients and healthy control subjects

An Overview of the Therapeutic Effects of Camel Milk in the Treatment of Type 1 Diabetes Mellitus

The main treatment of type 1 diabetes mellitus (DM) is insulin replacement via parenteral routes, which is far fromsatisfactory. Camel milk is an alternative to current insulin treatment. This paper discusses the chemical constituentsand properties of camel milk, recent experimental evidences about the effectiveness of camel milk in the treatmentof insulin dependent diabetes mellitus, role of the camel milk in the restoration of damaged beta-cells of thepancreas and in the improvement of disturbed lipid metabolism associated with type 1 DM as well as the effects ofcamel milk in the improvement of clinical function parameters of the kidneys and liver of subjects with insulindependent diabetes mellitus. This paper demonstrates that, camel milk causes significant reduction in insulin dosages in insulindependentdiabetic subjects to obtain glycemic control along with significant improvement in HbA1c level, and improvement inmicro albuminuria. Significant improvements were also observed in lipid metabolism, body mass index (BMI),biochemical parameters of the liver and kidney functions of camel milk fed experimental subjects with type-1diabetes. Camel milk works as a regulator of blood sugar in the absence of original insulin, and it seems to worktogether with the body’s own restorative andregenerative abilities. Camel milk is well tolerated and its uses are notassociated with an increase in hypoglycemic events. Camel milk may be able to eliminate the alloxan and other chemicals’ induced-toxicity on pancreas and on other body organs via regenerative effects on damaged cells and could be used as a restorative treatment of diabetes.The main treatment of type 1 diabetes mellitus (DM) is insulin replacement via parenteral routes, which is far from satisfactory. Camel milk is an alternative to current insulin treatment. This paper discusses the chemical constituents and properties of camel milk, recent experimental evidences about the effectiveness of camel milk in the treatment of insulin dependent diabetes mellitus, role of the camel milk in the restoration of damaged beta-cells of the pancreas and in the improvement of disturbed lipid metabolism associated with type 1 DM as well as the effects of camel milk in the improvement of clinical function parameters of the kidneys and liver of subjects with insulin dependent diabetes mellitus.This paper demonstrates that, camel milk causes significant reduction in insulin dosages in insulin dependent diabetic subjects to obtain glycemic control along with significant improvement in HbA1c level, and improvement in micro albuminuria. Significant improvements were also observed in lipid metabolism, body mass index (BMI),biochemical parameters of the liver and kidney functions of camel milk fed experimental subjects with type-1diabetes. Camel milk works as a regulator of blood sugar in the absence of original insulin, and it seems to work together with the body’s own restorative and regenerative abilities. Camel milk is well tolerated and its uses are not associated with an increase in hypoglycemic events. Camel milk may be able to eliminate the alloxan and other chemicals’ induced-toxicity on pancreas and on other body organs via regenerative effects on damaged cells and could be used as a restorative treatment of diabetes.

Effect of Supplementation of Tulsi (Ocimum sanctum) and Neem (Azadirachta indica) Leaf Powder on Diabetic Symptoms, Anthropometric Parameters and Blood Pressure of Non Insulin Dependent Male Diabetics

The incidence of diabetes is increasing all over the world affecting more than 246 million people. Ninety non insulin dependent male diabetic subjects in the age group of 40-60 years were selected from PAU, Ludhiana to study the effect of supplementation of tulsiand neemleaves on the signs and symptoms anthropometric parameters and blood pressure of the diabetic subjects. General information of the subjects was recorded by interview schedule. After one month control period ninety subjects were divided into three groups of 30 each. Group I was given tulsileaf powder, group II was given neemleaf powder and group III given mixture of both leaf powder in the form of capsules. Daily dosage of four capsules i.e. 2 g powder (Lunch and dinner) was given and supplementation was carried out for a period of 3 months. The most common symptoms of diabetes observed in diabetic patients were polydypsia, polyurea, polyphagia and tiredness. Some other symptoms were sweating, burning feet, itching and headache. Significant reduction in all the diabetic symptoms was observed in all the three groups but maximum reduction was seen in group III patient who were given mixture of tulsiand neemleaf powder. Significant percent reduction in the symptoms like polydypsia (35, 33, 40), polyphagia (21, 35, 40) and headache (27, 38, 40) was observed in group I, II and III respectively. It can be concluded from the study that tulsiand neemleaves are helpful in reducing the diabetic symptoms and blood pressureof the subjects. Non significant improvement in the anthropometric parameters of the subjects was observed after supplementation of tulsi and neem leaves powder of the patients. Therefore these leaves should be regularly consumed by the diabetic patients to get relief from the diabetic symptoms.

Effect of Stevia Leaf (Stevia rebaudiana) Powder Supplementation and Nutrition Counselling on Anthropometric Parameters and Gain in Knowledge of the Subjects

KEYWORDS Anthropometric parameters; knowledge; nutrition counselling; stevia leaf powder; supplementation ABSTRACT Ninety non insulin dependent male diabetic subjects between 40-50 years, free from serious complications were selected from Punjab Agricultural University (PAU) hospital, Ludhiana to study the effect of supplementation of stevia leaf powder and nutrition counselling on anthropometrics parameters and gain in knowledge of non insulin dependent diabetics. The subjects selected were divided into three groups namely group I, group II and group III having thirty subjects each. Group I subjects were only given medicine prescribed by the doctor, group II subjects were given medicine prescribed by the doctor and nutrition counselling and group III subjects were given medicine, nutrition counselling and stevia leaf powder. One gm of stevia leaf powder was incorporated in 500 mg capsules and were given to the subjects daily during breakfast and lunch for three months. Nutrition education was given to the subjects of group II and III for 3 months after fifteen days interval. It was observed that majority of the subjects in all the three groups had craving for sweet foods, liked fried foods. Frequency of consumption of vegetables and fruits by the subjects was increased in Group II and III after nutrition counselling. Physical activity pattern of the subjects of Group II and III was increased after nutrition counselling, significant decrease in weight of the subjects of Group II and III was observed. It was seen that there was a significant increase in knowledge, attitude and practices and hence gain in total knowledge of subjects in Group II and III after three months of the study. While there was a non-significant increase in the knowledge of the subjects of Group I. Hence it can be inferred from the results that supplementation of stevia leaf powder along with nutrition counselling significantly improved the nutritional status of diabetic patients

Effect of Stevia Leaf (Stevia rebaudiana) Powder Supplementation and Nutrition Counselling on Anthropometric Parameters and Gain in Knowledge of the Subjects

KEYWORDS Anthropometric parameters; knowledge; nutrition counselling; stevia leaf powder; supplementation ABSTRACT Ninety non insulin dependent male diabetic subjects between 40-50 years, free from serious complications were selected from Punjab Agricultural University (PAU) hospital, Ludhiana to study the effect of supplementation of stevia leaf powder and nutrition counselling on anthropometrics parameters and gain in knowledge of non insulin dependent diabetics. The subjects selected were divided into three groups namely group I, group II and group III having thirty subjects each. Group I subjects were only given medicine prescribed by the doctor, group II subjects were given medicine prescribed by the doctor and nutrition counselling and group III subjects were given medicine, nutrition counselling and stevia leaf powder. One gm of stevia leaf powder was incorporated in 500 mg capsules and were given to the subjects daily during breakfast and lunch for three months. Nutrition education was given to the subjects of group II and III for 3 months after fifteen days interval. It was observed that majority of the subjects in all the three groups had craving for sweet foods, liked fried foods. Frequency of consumption of vegetables and fruits by the subjects was increased in Group II and III after nutrition counselling. Physical activity pattern of the subjects of Group II and III was increased after nutrition counselling, significant decrease in weight of the subjects of Group II and III was observed. It was seen that there was a significant increase in knowledge, attitude and practices and hence gain in total knowledge of subjects in Group II and III after three months of the study. While there was a non-significant increase in the knowledge of the subjects of Group I. Hence it can be inferred from the results that supplementation of stevia leaf powder along with nutrition counselling significantly improved the nutritional status of diabetic patients

Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients.

Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.

Nutrient Adequacy of Non Insulin Dependent Male Diabetics Influenced by Nutrition Counseling

Sixty non insulin dependent male diabetic subjects in the age group of 40-60 years were selected from hospital of Punjab Agricultural University, Ludhiana and were surveyed for their nutrient adequacy using 24 hour recall method for three consecutive days. Nutrition education was imparted to the subjects after assessing their basic knowledge regarding the di et and disease. Nutrition counseling improved their mean score of diabetic knowledge significantly (P <0.01) from 7.31 to 19.26. Significant decrease in the consumption of cereals, milk and milk products, fats and oils, sugar and jaggery whereas increase i n the consumption of pulses, green leafy vegetables, root vegetables was found among diabetics after nutrition counseling. The percen tage of calories from carbohydrates 59 to 61%, protein 13 to 16% increased and from fat it was decreased to 27 to 22% in the subject s after nutrition counseling. The intake of fiber (39 to 44%) increased while of vitamins and minerals except iron, zinc and niac in were adequate in the subjects after nutrition counseling as compared to ICMR's recommendations. Thus, nutritional counseling is an effective measure to bring about the favourable and significant change in diabetic state.

Impact of Nutrition Counseling and Supplementation of Medicinal Plants on the Anthropometry and Blood Pressure of the Diabetic Subjects

Sixty non insulin dependent male diabetic subjects were selected from PAU Hospital, Ludhiana. Selected subjects were divided into two categories according to their grades of obesity i.e. overweight and normal weight to take their anthropom etric measurements. After assessing the basic knowledge of the subjects about the disease by knowledge testing questionnaire, the subjects were imparted nutrition education regarding the disease, its symptoms, causes, complications and dietary modifications . Supplementation of three medicinal plants namely bittergourd, jamun seeds and fenugreek seeds was done along with nutrition education. These plants were dried, powdered and mixed in equal proportions and two gram of this mixture was given to the subjects for a period of 3 months. The height, weight, mid upper arm circumference, tricep skinfold thickness and BMI of the subjects was measured before and after experimental period. A significant decrease in weight (74.3 to 70.14 kg), body mass inde x (27.47 to 25.84 kg/m) and MUAC (27.69 to 25.70 cm) was observed in overweight subjects and there was increase in the percentage (65 to 82%) of normal weight subjects having BMI between 20-25. The mean systolic (136 to 123 mm Hg) and diastolic (90 to 83 mm Hg) blood pressure decreased significantly (P <0.05) after intervention. Hence, it can be said that supplementation of these traditional medicinal plants and nutrition counseling is an effective measure to bring about favourabl e and significant changes in anthropometry of the diabetic subjects.

Gastric Electrical Stimulation Results in Improved Metabolic Control in Diabetic Patients Suffering From Gastroparesis

Symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. Gastric electrical stimulation (GES) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. However, the effect of GES on metabolic control has not been assessed yet. We performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy GES on symptoms, gastric emptying (measured scintigraphically), and metabolic control (HbA1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. Seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. No therapy-associated adverse events occurred. Weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. Gastric retention rates improved significantly from 83 % (2 h) and 38 % (4 h) to 35 % (2 h)/14 % (4 h) and 25 % (2 h)/17 % (4 h) at 6 and 12 months, respectively. HbA1c values were lowered in all 17 subjects; initially, all HbA1c values were above 7.5 %; at 6 and 12 months, mean values had significantly decreased from 8.6 % to 6.2 % and 6.5 %, respectively. Gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. This study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by HbA1c, a surrogate marker of the risk of diabetic complications.

Effect of weight reduction on the distribution of apolipoprotein A-I in high-density lipoprotein subfractions in obese non–insulin-dependent diabetic subjects

High-density lipoprotein (HDL) plays an important role in the process of reverse cholesterol transport, which may become suboptimal with increasing body fatness. HDL cholesterol that is reduced in obese subjects paradoxically decreases during weight reduction. To determine how weight reduction affects HDL subclasses that are involved in reverse cholesterol transport, we studied HDL from obese diabetic subjects before and after energy restriction within background diets high in either carbohydrate or monounsaturated fatty acids (MUFAs). Body weight, blood glucose, total cholesterol, and LDL cholesterol decreased after 8 and 12 weeks of weight reduction. With the very-low-fat diet, HDL cholesterol decreased significantly at 8 weeks, but recovered to initial levels after 12 weeks as body weight began to stabilize. Plasma apolipoprotein A-I (apo A-I) decreased substantially and significantly at 8 and 12 weeks with both diets, and was reflected in the reduction of apo A-I in HDL subclasses α1, α2, pre-β1, and pre-β2 + pre-β3. The calculation of the percentage distribution of apo A-I among HDL species showed that only the proportion of pre-β1-HDL decreased, whereas α2-HDL increased. This led to a significant increase in the α1 + α2/pre-β ratio, ie, the ratio of the large cholesterol ″storage” or ″sink” HDL to the HDL ″shuttle” fraction considered to be the initial acceptor of cell cholesterol. These data suggest that despite the reduction in HDL cholesterol and apo A-I, the redistribution of apo A-I in pre-β1-HDL and α-HDL observed with weight reduction appears to revert to the pattern that we have previously reported in lean as opposed to overweight subjects. Copyright © 2000 by W.B. Saunders Company

Mass concentration of plasma phospholipid transfer protein in normolipidemic, type IIa hyperlipidemic, type IIb hyperlipidemic, and non-insulin-dependent diabetic subjects as measured by a specific ELISA.

Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples (r=0.787, P<0.0001), did not differ between normolipidemic subjects (3.95+/-1.04 mg/L and 575+/-81 nmol. mL-1. h-1, respectively; n=30), type IIa hyperlipidemic patients (4. 06+/-0.84 mg/L and 571+/-43 nmol. mL-1. h-1, respectively; n=36), and type IIb hyperlipidemic patients (3.90+/-0.79 mg/L and 575+/-48 nmol. mL-1. h-1, respectively; n=33). No significant correlations with plasma lipid parameters were observed among the various study groups. In contrast, plasma concentrations of the related cholesteryl ester transfer protein (CETP) were higher in type IIa and type IIb patients than in normolipidemic controls, and significant, positive correlations with total and low density lipoprotein cholesterol levels were noted. Interestingly, plasma PLTP mass concentration and plasma phospholipid transfer activity were significantly higher in patients with non-insulin-dependent diabetes mellitus (n=50) than in normolipidemic controls (6.76+/-1. 93 versus 3.95+/-1.04 mg/L, P<0.0001; and 685+/-75 versus 575+/-81 nmol. mL-1. h-1, P<0.0001, respectively). In contrast, CETP levels did not differ significantly between the 2 groups. Among non-insulin-dependent diabetes mellitus patients, PLTP levels were positively correlated with fasting glycemia and glycohemoglobin levels (r=0.341, P=0.0220; and r=0.382, P=0.0097, respectively) but not with plasma lipid parameters. It is proposed that plasma PLTP mass levels are related to glucose metabolism rather than to lipid metabolism.

Impairment of Ventilatory Response to Metabolic Acidosis in Insulin-Dependent Diabetic Patients with Advanced Nephropathy

Sudden cardiopulmonary arrest due to a defective respiratory reflex is observed in diabetic patients. Impaired ventilatorp response in diabetic patients to acute hypoxia or hypercapnia induced by the inhalation of an artificial gas has been reported. Little is known regarding the respiratory compensatory ability for mild to moderate metabolic acidosis due to renal failure in insulin-dependent diabetic subjects. Arterial blood pH, HCO3, PaCO2 and PaO2 were measured in 13 insulin-dependent diabetic subjects with advanced nephropathy and in 33 non-diabetic subjects with end-stage renal failure. The diabetic group consisted of six predialysis patients and seven on regular hemodiaiysis (HD), md the non-diabetic group, ten predialysis patients and 23 on HD. Differences between measured partial arterial pressure of carbon dioxide (PaCO2) and predicted PaCO2 determined fiom HCO3 were examined. PaCO2 was significantly higher in the diabetic than in non-diabetic group (40.0 ± 7.4 versus 31.1 ± 5.1 mmHg, p < 0.05 in predialysis, 42.0 ± 6.4 versus 36.0 ± 2.6mmHg, p < 0.05 in HD), though plasma pH was essentially the same for either. Differences in measured PaCO2 and predicted PaCO2 were significantly larger in the diabetic group than in non-diabetic group. Ventilatoly respose to uremic acidosis may thus be considered impaired in subjects with advanced diabetic nephropathy.

Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

Regression and progression of cardiac sympathetic dysinnervation complicating diabetes: An assessment by C-11 hydroxyephedrine and positron emission tomography

Cardiovascular denervation complicating diabetes has been implicated in sudden cardiac death potentially by altering myocardial electrical stability and impairing myocardial blood flow. Scintigraphic evaluation of cardiac sympathetic integrity has frequently demonstrated deficits in distal left ventricular (LV) sympathetic innervation in asymptomatic diabetic subjects without abnormalities on cardiovascular reflex testing. However, the clinical significance and subsequent fate of these small regional defects is unknown. This study reports the results of a prospective observational study in which positron emission tomography (PET) with (—)-[ 11C]- meta-hydroxyephedrine ([ 11C]-HED) was used to evaluate the effects of glycemic control on the progression of small regional LV [ 11C]-HED retention deficits in 11 insulin-dependent diabetic subjects over a period of 3 years. The subjects were divided into two groups based on attained glycemic control during this period: group A contained six subjects with good glycemic control (individual mean HbA1c < 8%), and group B contained five subjects with poor glycemic control (individual mean HbA1c ≥ 8%). Changes in regional [ 11C]-HED retention were compared with reference values obtained from 10 healthy aged-matched nondiabetic subjects. At baseline, abnormalities of [ 11C]-HED retention affected 7.3% ± 1.4% and 9.9% ± 6.6% of the LV in group A and B subjects, respectively, with maximal deficits of LV [ 11C]-HED retention involving the distal myocardial segments. At the final assessment in group A, the extent of the deficits in [ 11C]-HED retention decreased to involve only 1.7% ± 0.7% of LV ( P < .05 v baseline scan), with significant increases in [ 11C]-HED retention occurring in both the distal and proximal myocardial segments. In contrast, in group B with poor glycemic control, the extent of [ 11C]-HED deficits increased to involve 34% ± 3.5% of the LV ( P < .01 v baseline), with retention of [ 11C]-HED significantly decreasing in the distal segments ([ 11C]-HED retention index, 0.066 ± 0.003 v 0.057 ± 0.002, P < .05, at baseline and final assessment, respectively). Poor glycemic control was associated with increased heterogeneity of LV [ 11C]-HED retention, since three of five group B subjects developed abnormally increased [ 11C]-HED retention in the proximal myocardial segments. In conclusion, defects in LV sympathetic innervation can regress or progress in diabetic subjects achieving good or poor glycemic control, respectively. In diabetic subjects with early cardiovascular denervation, institution of good glycemic control may prevent the development of myocardial sympathetic dysinnervation and enhanced cardiac risk.

Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling.

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns.

Effects of perindopril on renal histomorphometry in diabetic subjects with microalbuminuria: A 3-year placebo-controlled biopsy study

We conducted a 3-year randomized placebo-controlled double-blind study to determine the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the progress of renal function and histology in subjects with diabetes and microalbuminuria. Forty non—insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetic subjects, either normotensive or hypertensive, were randomly assigned to receive PE (n = 20) or placebo (n = 20). A percutaneous renal biopsy was performed initially in all patients and repeated in 29 patients after 3 years. The mean glomerular volume, glomerular basement membrane (GBM) thickness, interstitial fibrosis, sclerosed glomeruli, and volume fraction of capillary lumina were measured histomorphometrically. Before treatment, both groups had similar clinical characteristics, blood pressure, glycosylated hemoglobin (Hb), albumin excretion rate, glomerular filtration rate (GFR), serum creatinine, and renal structural damage. Blood pressure was well controlled in both groups. After 3 years' therapy, there was no significant change in renal function and albuminuria in the PE or placebo groups. The increase in GBM thickness in nine paired biopsies was significantly less in PE-treated subjects ( P = .0275). Interstitial fibrosis tended to increase less in the PE group, although this did not reach statistical significance. This study indicates that long-term therapy with PE may decrease or delay the progression of structural glomerular damage in microalbuminuric diabetic subjects.

Lipolytic response during spontaneous hypoglycaemia in insulin-dependent diabetic subjects.

The adipose tissue lipolytic response to spontaneous, non-experimental hypoglycaemic episodes was investigated in patients with IDDM during ordinary life conditions. The absolute concentration of glucose and glycerol in subcutaneous adipose tissue was monitored in mobile patients with microdialysis in 16 IDDM subjects. The absolute glycerol level in adipose tissue was about five times as high as in venous plasma, whereas the glucose concentration was almost the same in the two compartments. Fourteen hypoglycaemic episodes (glucose < 3.5 mmol/l) were recorded. Adipose tissue glycerol increased markedly by 75 % in response to hypoglycaemia and remained increased during at least 4 hours following glucose nadir (F = 3.70, p = 0.003). The circulating levels of free fatty acids increased about three-fold in parallel to the in situ lipolytic response (F = 2.98, p = 0.025). The same lipolytic response was observed whether or not the hypoglycaemic event was perceived by the patient. A rapid decrease in glucose concentration above hypoglycaemic levels did not affect the adipose tissue dialysate glycerol. It is concluded that spontaneous hypoglycaemia elicits a long-term lipolytic response in adipose tissue as evidenced by increased levels of glycerol in adipose tissue with a parallel increase in serum free fatty acids. However, lipolysis is not activated by a rapid glucose decrease per se. The microdialysis method can be used to characterise the lipolytic response to hypoglycaemic episodes in every day life of IDDM patients.

Serum antioxidant capacity in healthy and diabetic subjects as determined by enhanced chemiluminescence.

Free radicals are considered to be important factors involved in many physiopathological processes. Several methods have been proposed for studying the mechanisms of antioxidant protection against free radical-induced injury, including the measurement of the total antioxidant capacity (TAC) in body fluids, based on enhanced chemiluminescence. This technique is calibrated against Trolox and assay results are expressed as mumol/L of Trolox equivalents. Since many of the complications induced by diabetes appear to be mediated by oxygen free radical generation, we have investigated serum antioxidant capacity in a group of healthy subjects and in insulin-dependent diabetic (IDDM) subjects. A statistically significant difference was noticed in TAC values between the IDDM group and the young control group. Even if the biological meaning of this significant reduction in TAC remains to be explained, an overproduction of precursors of reactive oxygen free radicals and/or a decreased scavenger systems efficiency can be associated with the increased risk of atherosclerotic cardiovascular disease in diabetic patients.