Non-insulin-dependent Diabetes Mellitus Subjects Research Articles

Suitability of pearl millet (Pennisetum glaucum (L.) R. Br.) and sorghum (Sorghum bicolor (L.) Moench) based food products for diabetics

AbstractIn the study, suitability of porridge, bun, and salad prepared from processed pearl millet FBC16 and sorghum PSC4 had been evaluated organoleptically by a panel of semi-trained judges and 25 non-insulin dependent diabetes mellitus subjects. Organoleptically, germinated pearl millet was found to be more suitable for porridge (50%) and salad (100%), while puffed sorghum was best suitable for bun (15%) preparation. Prepared porridge had significantly (P ≤ 0.05) higher protein (16.9%) and total phenols (178.8 mg GAE/100 g) contents and antioxidant capacity (1,036 mg TE/100 g) than control. The dietary fibre and in vitro starch digestibility of composite porridge and bun increased significantly (P ≤ 0.05). Most acceptable composition of porridge, bun, and salad had low glycaemic index (17.64–26.79) and medium to low glycaemic load (8.82–13.40). Suitability of pearl millet and sorghum using appropriate processing techniques (germination and puffing) is recommended for preparation of indigenous food products especially for diabetics.

Impact of a particular diet on the nutritional status and glycemic response of noninsulin-dependent diabetes mellitus patients – An analytical study

BACKGROUND: Diabetes mellitus is a heterogeneous primary disorder of carbohydrate metabolism with multiple etiological factors that generally involve absolute or relative insulin deficiency or insulin resistance or both. All causes of diabetes ultimately lead to hyperglycemia, which is the hall mark of this disease syndrome. Nutrition and diet play a critical role in the course of disease, in the controlling hyperglycemia in addition to drugs in diabetes mellitus patients.OBJECTIVES: To assess nutritional status of noninsulin-dependent diabetes mellitus (NIDDM) patients and glycemic response to the given type of food as compared to normal individuals.MATERIALS AND METHODS: Out of 40 cases of NIDDM patients, 15 normal subjects belonging to the same age and socioeconomic group were selected for the study on glycemic response to dextrose load and given test food (idly). In another six of NIDDM subjects, glycemic response to test food chapati was studied. In 13 cases of diabetes with hypertension, 12 cases of diabetes without hypertension, and 16 cases of normal subjects, a wide range of biochemical parameters like lipid profile, free fatty acid (FFA) levels, serum, and erythrocyte copper and malondialdehyde levels were estimated among them.DISCUSSION: The results of the study showed that in NIDDM patients, body mass index is significantly lower than the normal, showing that obesity is not a predisposing condition in these subjects. The glycemic response to food (idly) is much higher than the response observed in normal subjects. The extent of suppression and FFA levels in the serum that was brought out by the food for glucose is lower than that observed in normal subjects.CONCLUSION: High lipid profile values and low copper levels can favor the generation of lipid-derived free radicals, which further predispose to the vascular changes and hypertensive states observed in the NIDDM patients.

Yoga-asanas and pranayama: Is it helpful in management non-insulin-dependent diabetes mellitus

Background: Deficiency of insulin generally causes diabetes mellitus (DM), a metabolic disorder with elevated blood glucose levels. Practicing yoga and pranayama affects the secretion of insulin and glucagon through neurohormonal modulation. Objectives: The objectives of the study were to see 16 weeks yoga-asanas and pranayamas helpful in non-insulin-dependent DM (NIDDM) (Type II DM) management. Materials and Methods: A total of 50 participants of both gender between 35 and 60 years of age with NIDDM (Type II DM) subjects of at least 12 months duration, those on antidiabetic diet and oral hypoglycemic medicine were included in the study. After recording the baseline parameters (pre-intervention values), yoga and pranayama was practiced by all the participants once in a day, daily for 16 weeks. Blood sample for fasting blood sugar (FBS), post-prandial blood sugar (PPBS), glycosylated hemoglobin A1C (HbA1C), and hemoglobin (Hb) was estimated at day 1 and at the end of each of the 4 months of the study period. After 16 weeks values were compared and analyzed. Results: Decreased FBS and PPBS values from 139.2 ± 16.6 and 174.1 ± 7.9 mg/dl to 96.8 ± 15.9 and 134.7 ± 8.4 mg/dl, respectively. HbA1C value decreased from 9.3 ± 1.0 to 6.9 ± 0.7. Hb value increased from 10.2 ± 1.3 to 12.6 ± 1.6. Conclusion: Our study provides yoga-asanas and pranayamas helpful in the NIDDM (Type II DM) management.

Telomere mean length in patients with diabetic retinopathy.

Telomere regression has been shown to be associated with several complex disorders like diabetes mellitus, cancer, cataract etc. Diabetic retinopathy develops as a complication of chronic hyperglycemia leading to increased oxidative stress that may potentially lead to shortening of telomeres. We sought to determine whether there is any association between telomere mean length (TML) of peripheral blood monocytes with the presence and severity of diabetic retinopathy. The study involved 120 subjects, comprising 27 non-insulin dependent diabetes mellitus (NIDDM) without any diabetic retinopathy (NDR), 45 NIDDM subjects with non-proliferative diabetic retinopathy (NPDR), 12 NIDDM subjects with proliferative diabetic retinopathy (PDR) and 36 healthy controls. Determination of TML of the study subjects was performed by Southern hybridization using telomere probe. Among the biochemical parameters, HBA1c showed a negative correlation with shortened telomeres in the PDR subjects. However, telomere length was positively correlated with high density lipo protein (HDL) in the control subjects. The control group had significantly greater TML as compared to the rest of the groups and the NDR subjects with NPDR and PDR had substantially decreased TML than the NIDDM subjects without retinopathy.

Audiovestibular functions in noninsulin-dependent diabetes mellitus

Conclusion: This study supports the proposition that vestibular dysfunction and sensorineural hearing loss (SNHL) may be considered among the complications due to noninsulin-dependent diabetes mellitus (NIDDM). Objective: The aim of this study was to evaluate the audiovestibular functions in patients with NIDDM and to determine if there is any correlation between audiovestibular dysfunction and the duration of the disease. Methods: A total of 104 patients diagnosed with NIDDM and 104 nondiabetic control subjects made up the study group. Diabetic patients were also divided into subgroups of ≤7 years and >7 years according to the duration of the disease. Pure-tone audiometry (PTA), speech recognition scores (SRS), impedance audiometry, and vestibular function tests (VFT) were performed for all of the patients. Results: Hearing thresholds in all frequencies (except at 500 Hz for bone conduction) and SRS values were statistically significant in patients with NIDDM and control subjects, but there was no statistically significant difference according to the duration of the disease. Statistically significant alterations were present in VFT in patients with NIDDM compared with the control subjects. In the diabetic group, only failure in the saccade test was statistically significant according to the duration of the disease.

Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in non insulin dependent diabetes mellitus induced rats

Objective:To study the effect of Trichosanthes cucumerina Linn. on non insulin dependent diabetes mellitus induced rats.Materials and Methods:Non Insulin Dependent Diabetes Mellitus (NIDDM) was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. NIDDM animals were treated with aqueous extract of Trichosanthes cucumerina (100 mg/kg/day) orally for six weeks. Parameters such as fasting blood glucose, Oral Glucose Tolerance Test (OGTT) and tissue glycogen content were evaluated.Results:Aqueous extract of Trichosanthes cucumerina significantly (P<0.01) decreased the elevated blood glucose of NIDDM induced rats. OGTT of NIDDM animals showed glucose intolerance. Blood glucose of diabetic animals reached peak at 45 min and remains high even after 2h. In case of Trichosanthes cucumerina treated group, the blood glucose reached peak level at 30 min, followed by decrease in glucose level up to 2h. The drug has significantly (P<0.01) reduced the postprandial blood glucose of diabetic animals. Glycogen content of insulin dependent tissues such as liver and skeletal muscle was found to be improved by 62% and 58.8% respectively with Trichosanthes cucumerina as compared to NIDDM control.Conclusion:Studies revealed that, Trichosanthes cucumerina possess antidiabetic activity. The drug improved the oral glucose tolerance of NIDDM subjects. Increase in tissue glycogen content indicates the effect of the drug on the uptake of glucose by the peripheral tissues to reduce insulin resistance of NIDDM.

Body Fat Distribution and Blood Pressure according to Anthropometric Change in Korean Patients with Non-Insulin Dependent Diabetes Mellitus(NIDDM)

This study was done to identify fat distribution and blood pressure according to anthropometric change patterns between NIDDM patients and control subjects. Cross-sectionally 167 NIDDM patients and 87 controls were studied. Previous maximal body weight and acute weight loss was obtained. Current height, body weight, BMI, waist-hip ratio (WHR), skinfold thicknesses(abdomen, subscapular and triceps), and blood pressure was measured. Three anthropometric change patterns were categorized by BMI changes from the maximum lifetime's BMI to the current time (obese-obese, obese-nonobese and nonobese-nonobese: obese: BMI > or =25 kg/m2, nonobese: BMI<25 kg/m2). The data was analyzed by Chi2, t-test, age adjusted ANCOVA and Least Squares Means (LSM) for multiple comparison. Acute body weight loss (p=0.01), anthropometric change types (p=0.001), WHR (P=0.05), and skinfold thickness (p=0.002) of NIDDM were significantly higher than those of the controls. The mean arterial pressure, WHR and skinfold thicknesses were greater in both obese-obese and obese-nonobese NIDDM and control subjects compared with both nonobese-nonobese NIDDM and control subjects. (all p's<0.05). NIDDM patients had more central and upper body adiposicity. Also both obese-obese and obese-nonobese NIDDM and control subjects had higher mean arterial pressures and central body obesity.

Endogenously generated reactive oxygen species reduce PMCA activity in platelets from patients with non-insulin-dependent diabetes mellitus

Intracellular Ca2+ homeostasis in platelets of patients with non-insulin-dependent diabetes mellitus (NIDDM) has been reported to be altered, leading to an increased adhesiveness and spontaneous aggregation. Among the disturbed Ca2+ mechanism in platelets from NIDDM subjects, a reduced Ca2+ extrusion by the plasma membrane Ca2+-ATPase (PMCA) is especially relevant, maintaining an elevated cytosolic free Ca2+ concentration that results in platelet hypersensitivity. Here we show that treatment of platelets from NIDDM patients with 300 U/mL catalase or 5 mM D-mannitol, which prevent H2O2- and hydroxyl radicals-mediated oxidative stress, respectively, increases Ca2+ extrusion after treatment with thapsigargin (TG) plus ionomycin (Iono). In contrast, 1 mM trolox, a scavenger of ONOO–, did not alter TG + Iono-induced response. Catalase and D-mannitol reversed the enhanced tyrosine phosphorylation of PMCA induced by TG + Iono in NIDDM patients. These findings open up new horizon for the development of therapeutic strategies to palliate cardiovascular disorders in NIDDM.

Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children

Slowly progressing insulin-dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA-DRB1, -DQB1 and -DQA1 alleles, phenotypes, and genotypes and compared them with acute-onset type 1 diabetes, non-insulin-dependent diabetes mellitus (NIDDM), and control subjects. HLA-DRB1, -DQA1, and -DQB1 types were defined by DNA analysis using polymerase chain reaction (PCR), and typing for human leukocyte antigen (HLA) was performed by the sequencing-based typing (SBT) method using Match Maker and MT Navigator in combination. HLA-A24 was determined by the PCR-sequence-specific oligo-nucleotide probe (PCR-SSOP) method. The 234 patients with type 1 diabetes were divided into three groups: 32 cases of IDDMS, 137 cases of acute-onset form aged more than 5 yr (IDDMA), and 65 cases of acute-onset form less than 5 yr of age at onset (IDDME). In addition, we studied 55 children with type 2 diabetes (NIDDM) and 97 normal controls. The patients with IDDMS were older at diagnosis and had a greater body mass index (BMI) than those with IDDM (A + E). The prevalence of islet autoantbodies was not significantly different from IDDMA. The allele frequencies of DRB1*0405, DQA1*0302, and DQB1*0401 were significantly increased; however, DRB1*0901, DQA1*03, DQB1*0303, and HLA-A24 were low and not significantly different from control subjects. HLA phenotypes and genotypes in patients with IDDMS were different from those in NIDDM and control subjects and were closer to those of IDDMA. Together with a low prevalence of HLA-A24, the genetic features are similar to those of SPIDDM and latent autoimmune diabetes in adults (LADA) in adults. In our series, the clinical features such as lack of obesity and lack of responsiveness to oral hypoglycemic agents were most different from those of adults' onset.

Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate

Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.

Impairment of sodium pump and Na/H exchanger in erythrocytes from non-insulin dependent diabetes mellitus patients: effect of tea catechins

Background Tea catechins (EGCG, EGC, ECG and EC) possess many important biological properties. We evaluated the effect of tea catechins on erythrocyte membrane Na +/K +-ATPase and sodium/hydrogen exchanger (NHE) activity in normal (control) and NIDDM subjects. Methods Erythrocyte membrane Na +/K +-ATPase and NHE activity were determined in normal and non-insulin dependent diabetes mellitus (NIDDM) patients. In vitro effect of tea catechins was studied by incubating membrane/intact erythrocytes in assay medium prior to Na +/K +-ATPase/NHE activity determination. Results A 24.2% decrease in the activity of Na +/K +-ATPase ( p<0.001) and 39.37% increase in activity of NHE ( p<0.02) were observed in NIDDM subjects compared to normal. Tea catechins inhibited the activity of Na +/K +-ATPase and NHE in both normal and NIDDM erythrocytes, the effect was concentration-dependent. The inhibitory effect of EGCG and ECG at micromolar concentrations was greater compared to EGC and EC on Na +/K +-ATPase. On NHE the inhibition of tea catechins was in the order: EC>EGC>ECG>EGCG at concentrations up to 10 μmol/l. Conclusions This data may help to explain the anti-carcinogenic and cardioprotective effects of tea catechins. The effect of tea catechins on Na +/K +-ATPase and NHE may be explained due to a direct effect of these compounds on plasma membrane leading to a change in membrane fluidity.

Surface expression of fatty acid translocase (FAT/CD36) on platelets in myeloproliferative disorders and non-insulin dependent diabetes mellitus: effect on arachidonic acid uptake.

Increased platelet reactivity has been implicated in the vascular complications of myeloproliferative diseases and diabetes mellitus. The mechanisms of platelet hyperresponsiveness have not been fully explained. Expression of CD36 or fatty acid translocase (FAT) and its role in arachidonic acid (AA) uptake by platelets were examined in subjects with myeloproliferative disorders (MPD), those with non-insulin-dependent diabetes mellitus (NIDDM), and in normal, healthy, age-matched controls. Surface expression of CD36 on platelet membranes was increased in MPD (10.94 +/- 0.76 pmol/mg protein) compared with normal controls (6.94 +/- 0.48 pmol/mg protein), p < 0.001. Total platelet content of CD36 was also significantly higher (32.1 +/- 0.61 pmol/mg protein, p < 0.01) compared with those in sex and age matched normal controls (25.7 +/- 1.09 pmol/mg protein). In contrast, platelet surface expression of CD36 in NIDDM (6.5 +/- 0.56 pmol/mg protein) was not significantly different from those of normal controls despite higher total content of CD36 (32.8 +/- 1.2, pmol/mg protein, p < 0 .01). Intact MPD platelets bound significantly more arachidonic acid (AA) (1.53 +/- 0.16 nmol/mg protein, p < 0.05), compared with controls (1.12 +/- 0.07 nmol/mg protein) or NIDDM subjects (1.16 +/- 0.16 nmol/mg protein). The capacity of MPD platelet membranes to bind 14C-AA was also increased (1.72 +/- 0.25 nmol/mg protein, p < 0.05) compared with that of controls (1.62 +/- 0.05 nmol/mg protein) and of NIDDM (1.22 +/- 0.08 nmol/mg protein). This is consistent with higher surface expression of CD36 in MPD platelets. Membrane fatty acid analysis indicated that the % of AA in platelet phospholipids was significantly lower in MPD (3.15 +/- 0.81%) compared with the controls (5.62 +/- 1.7%, p < 0.05. The AA content of diabetic platelets (4.82 +/- 1.1%) was not significantly different from normal controls. In summary, both total and surface expression of CD36 are increased in MPD, consistent with an enhanced capacity for uptake of AA by platelets. Increased expression of CD36 in platelets may play a role in the vaso-occlusive manifestations of MPD.

Polymorphisms in the von Willebrand Factor Gene Are Not Associated with Proliferative Retinopathy in Non-Insulin-Dependent Diabetes mellitus

Von Willebrand factor, a multimeric glycoprotein synthesized mainly by endothelial cells, is involved in platelet adhesion and aggregation and has an important role in the process of angiogenesis. Increased levels of von Willebrand factor, reflecting activation or damage of endothelial cells, have been described in association with proliferative diabetic retinopathy (PDR). We investigated the relationships of two polymorphisms (–1793G/C and Thr789Ala) in the von Willebrand factor gene with PDR. Genotypes were detected by polymerase chain reactions with subsequent restrictions with specific endonucleases. Allele frequencies were determined in an association study (n = 371) comprising three groups of subjects (diabetics with and without retinopathy and nondiabetics). Allele frequencies of the –1793G/C and Thr789Ala did not differ between the non-insulin-dependent diabetes mellitus (NIDDM) + PDR and the NIDDM non-PDR groups (p > 0.05). However, a statistically significant difference in allele and genotype frequencies of the –1793G/C was proved between all NIDDM versus nondiabetic subjects (p = 0.024 and 0.0065, respectively) with allele G and genotype GG being significantly more frequent in the NIDDM group. Calculated odds ratio for the GG genotype was 1.20 (95% CI, 0.77–1.86). Although significantly higher plasma von Willebrand factor antigen levels in NIDDM patients with PDR have been described in several studies, our findings indicate that no association exists between the two polymorphisms and PDR. However, the –1793G/C polymorphism might affect the risk of NIDDM.

Vestibulo-ocular, optokinetic and postural function in diabetes mellitus.

We compared vestibulo-ocular reflex, optokinetic reflex and postural function in subjects with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), as well as non-diabetic controls. Both IDDM and NIDDM subjects exhibited significant deficits in gaze-holding in darkness (p < 0.05), small changes in vestibulo-ocular reflex (VOR) phase re velocity (p < 0.005) without a change in VOR gain, and a decrease in optokinetic reflex (OKR) slow phase velocity (p < 0.001). In addition, a smaller decrease was found in OKR quick phase amplitude (p < 0.02); postural sway was increased in both diabetic groups (p < 0.05), although this was not specific to the conditions of the Clinical Test of Sensory Interaction and Balance (CTSIB) that test vestibular contributions to postural stability. No differences were found in optokinetic afternystagmus or latency to circularvection. These results suggest that both IDDM and NIDDM are associated with deficits in gaze-holding, VOR and OKR function.

Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease

Statement of the problem: Low levels of high-density lipoprotein cholesterol (HDL-C) have a strong association with coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. Methods: The separation of HDL subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant and its cholesterol content was measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference between results for total HDL cholesterol and HDL2 cholesterol. Results: NIDDM patients with CAD had significantly higher triglyceride levels compared to either control (217.09±55.04 versus 89.62±31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09±55.04 versus 156.28±46.39 mg/dl, P<.05). However, in the diabetic patients with CAD, there was a statistically significant decrease in HDL cholesterol (39.63±8.59 versus 55.86±13.49 mg/dl, P<.01), HDL2 cholesterol (8.74±3.28 versus 16.95±5.73 mg/dl, P<.001), and HDL3 cholesterol (31.23±7.41 versus 38.91±8.93 mg/dl, P<.05) in comparison to nondiabetic controls. Moreover, in the comparison between non-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63±8.59 versus 46.13±6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74±3.28 versus 11.84±4.01 mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were (31.23±7.41 versus 34.29±7.94 mg/dl, P=.92) unaltered. Additionally, the percentage reduction of cholesterol in HDL2 fraction was proportionately greater than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD subjects without NIDDM. Conclusions: In conclusion, HDL2 is the more variable subclass and reflects changes in HDL. This suggests that the protective role of total HDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary heart disease than total HDL, in non-insulin-dependent diabetes mellitus.

Duration of Non-Insulin-Dependent Diabetes mellitus and the TNF-β NcoI Genotype as Predictive Factors in Proliferative Diabetic Retinopathy

The object of the study was to investigate the share of the polymorphisms I/D ACE, endothelin 1 4127G/A and TNF-β NcoI in the susceptibility to proliferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mellitus (NIDDM). Genotypes were detected by polymerase chain reactions and determined in a set of 246 Caucasian NIDDM subjects with defined PDR status. The relevance of genotypes and clinical characteristics to the PDR occurrence was tested using multiple linear regression models and discrimination analysis. The best predictive value for PDR was given by a combination of two parameters – NIDDM duration and the TNF-β genotype (p < 1·10^–6 and p = 1·10^–2, respectively) with a correct retrograde prediction of 82.6%. A comparison of the TNF-β NcoI allele frequencies revealed no difference between NIDDM and nondiabetic subjects (n = 176), but a statistically significant difference was found between PDR and non-PDR NIDDM subjects (after a correction for the number of comparisons p = 0.03), allele β₂ being associated with PDR. Our results identified the allele variant TNF-β₂ being associated with PDR in NIDDM. Diabetes duration and the TNF-β NcoI genotype were proven to significantly predict PDR occurrence. The TNF-β₂ allele could be regarded as a separate genetic risk factor that increases the relative incidence of PDR in patients with NIDDM.

Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.

The high affinity sulfonylurea receptor 1 (SUR1) is involved in the metabolism of glucose in pancreatic beta-cells. We investigated the impact of the SUR1 intron 16-3t-->c polymorphism on non-insulin-dependent diabetes mellitus (NIDDM) prevalence in a large representative sample of French men and women, 35-64 years old, and explored potential relationships between the SUR1 intron 16 -t-->c polymorphism and sulfonylurea therapy efficiency. This study took place in Lille (northern), Strasbourg (eastern), and Toulouse (southern France). One hundred and twenty-two subjects with NIDDM were registered. We stratified NIDDM subjects according to their medical treatment: sulfonylureas (n = 70) versus other treatments (n = 50). From the three populations, a control group was selected (n = 1,250). Subjects carrying the cc intron 16 genotype had an increased risk of NIDDM [odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.10-2.80; P = 0.017]. Subjects bearing at least one -3c allele and treated with sulfonylurea agents had fasting plasma triglyceride concentrations 35% lower than subjects that were tt homozygous (P = 0.026), whereas no difference could be detected between genotypes in NIDDM subjects treated with other treatments. The SUR1 intron 16 -3t-->c polymorphism was associated with an increased susceptibility to NIDDM in this population study, and seems to modulate the sulfonylurea therapy efficiency on hypertriglyceridemia reduction. This observation may help to better target the various therapies available for treatment of NIDDM.

Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy.

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.

Diabetic state induces lipid loading and altered expression and secretion of lipoprotein lipase in human monocyte-derived macrophages

Non-insulin-dependent diabetes mellitus (NIDDM) is frequently associated with macroangiopathies and coronary heart diseases. Lipoprotein lipase (LPL), an enzyme known to undergo significant functional alterations in diabetic state, is also a potential atherogenic protein. Since, to the best of our knowledge, there are no data concerning LPL secreted by macrophages of NIDDM patients we conducted a study to assess the expression and activity of LPL secreted by monocyte-derived macrophages from NIDDM patients with cardiovascular complications versus cardiovascular patients without diabetes (controls). Isolated cells from NIDDM patients, after 7 days in culture in the presence of 20% autologous serum, readily exhibit a foam cell phenotype, in contrast to the cells from controls. Macrophages were mainly loaded with triglycerides, whose cellular amount was well correlated to triglyceridemia of NIDDM subjects. Concomitantly, macrophages from NIDDM patients displayed a ∼six-fold decrease of mRNA expression and a ∼two-fold reduction of the activity of secreted LPL, as compared to control cells. These data suggest that in complicated diabetic state, macrophage loading leading to foam cell formation is accelerated, at least in part, due to a diminished expression and activity of LPL. These observations add and extend the data that may explain the occurrence of accelerated atherogenesis and of the atherosclerotic complications associated with diabetes.

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes

OBJECTIVESThe present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM).BACKGROUNDAngiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function.METHODSThe influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography.RESULTSLosartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed.CONCLUSIONSLosartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.