International Journal of Diabetes Mellitus

Raising the priority accorded to diabetes in global health and development: A promising response…

Ala Alwan — 2010-11-15

On 13 May 2010, the United Nations General Assembly (UNGA) passed a resolution A/RES/64/265 on non-communicable diseases (NCDs). This step is of historic significance in global health and development, as the resolution recognizes the enormous human suffering, premature death and the seriously negative socioeconomic impact caused by NCDs .

Free radical activity in hypertensive type 2 diabetic patients

Suvarna Prasad, Ajay Kumar Sinha — 2010-11-08

Abstract: Background: Free radical activity is an important cause of vascular complications in type 1 diabetes mellitus. But data regarding vascular complications in type 2 diabetes mellitus are scant.Objectives: The aim of this study was to examine free radical activity in type 2 diabetic patients with hypertension compared to those without hypertension.Materials and Methods: The serum levels of lipid peroxidation product, MDA malondialdehyde), the free radical scavenger, SOD (superoxide dismutase) and NO (nitric oxide) were studied in 50 type 2 diabetic outpatients. Controls were regarded as those diabetic outpatients who did not have hypertension.Result: Among 50 patients thus studied 19 were hypertensive. The concentration (median (range)) of both SOD (21.31(5.33–26.64) vs. 16.65(6.66–22.64)U/dl; p<0.05) and NO (18.54 (11.40–37.07) vs. 21.39(15.69–35.65)U/dl; p<0.05) were reduced in the hypertensive group. Similarly, concentration (median (range) of MDA (359(231–718) vs. 385(256–666)μmoles/dl; p<0.01 were increased in the hypertensive group.Conclusion: The reduction in serum levels of SOD and NO with a concomitant increase in serum MDA levels is consistent with an increase in free radical activity in hypertensive type 2 diabetics.

Association of serum free IGF-1 and IGFBP-1 with insulin sensitivity in impaired glucose tolerance (IGT)

2010-10-04

Abstract: Aim and Background: Free IGF-1 and IGFBP-1 are associated with obesity which is one of the major features of insulin resistance. But very few studies exist on free IGF-1 and IGFBP-1 in IGT subjects. The present study was undertaken to investigate the association of free IGF-1 and IGFBP-1 with insulin sensitivity in IGT subjects. Subjects and Methods: Ninety-one subjects with impaired glucose tolerance (IGT) were studied along with age- sex- and BMI-matched sixty-one healthy Controls without family history of diabetes or prediabetes. Insulin, free IGF-1 and IGFBP-1 were measured by standard ELISA method. Insulin secretory capacity (HOMA B) and insulin sensitivity (HOMA S) were calculated using fasting glucose and fasting insulin by HOMA-CIGMA software. Results: Fasting free IGF-1 and IGFBP-1 levels were not significantly different among the study groups. In stepwise multiple regression analysis, when free IGF-1 was considered as a dependent variable with other independent variables, model 1 (β=−0.352, p=0.03), model 2 (β=−0.355, p=0.033) and model 5 (β=−0.378, p=0.026) have shown significant association of fasting glucose with free IGF-1. Similarly when IGFBP-1 was considered as a dependent variable, model 4 (β=−0.865, p=0.03) and model 5 (β=−0.1.07, p=0.004) have shown negative association of fasting glucose with IGFBP-1. In this analysis model 5 have also shown negative association of HOMA S with IGFBP-1 (β=−1.015, p=0.017). Conclusion: IGF1 and IGFBP-1 seems to be negatively associated with fasting glucose in IGT subjects and insulin sensitivity (HOMA S) may also be negatively associated with IGFBP-1 in IGT subjects.

The prevalence and incidence of and risk factors for, micro-albuminuria among urban Africans with type 1 diabetes in South Africa: An inter-ethnic study

W.J. Kalk, F.J. Raal, B.I. Joffe — 2010-11-09

Abstract: Background: Type 1 diabetes (T1DM) in sub-Saharan Africans is rare and is associated with high mortality from nephropathy. We studied the prevalence and potential risk factors for microalbuminuria (MA) in African and in age-of-onset matched white patients with T1DM. Risk factors for MA were evaluated prospectively in an African cohort.Materials and Methods: 68 African and 134 white patients, age at diagnosis 10–40 years, duration of diabetes > 2 years, were evaluated for MA; 48 Africans were followed prospectively.Results: Africans had shorter duration of diabetes (median, 8 years vs 11 years), higher HbA1c (10.62(SD 2.52)%, vs 9.02(2.44)%, lower cholesterol (4.45(1.04) vs 5.45(1.16)mmol/l), and fewer (23.5% vs 54.5%) had adolescent diabetes onset (p 0.0030 for each); the prevalence of MA was 39.7% and 24.6% respectively (p=0.0155). In multiple regression analysis MA was associated with mean HbA1c (p<0.0001), younger age at diagnosis (p=0.0060), SBP (p=0.0012) and African race (p=0.0287). Prospectively, Africans developing MA (45%) had higher mean HbA1c levels (p=0.0001), were more likely to have had adolescent onset of DM (33.3% vs 8.0%, p=0.0310) and lower BMI (p=0.0340); logistic regression revealed that higher HbA1c and SBP, and lower BMI predicted MA. Nine of 16 African subjects progressed to macroalbuminuria; they were characterised only by extremely poor glycaemic control (mean HbA1c, 13.49(2.00)%).Conclusions: Microalbuminuria, and severe hyperglycaemia, are common in diabetic Africans with short duration TIDM; MA may rapidly progress to macroalbumiuria. African race may be associated with increased susceptibility to diabetic nephropathy.

Association between socio-demographic factors and diabetes mellitus in the north of Iran: A population-based study

2010-10-11

Abstract: Objective: This study considers the prevalence of DM and some related factors among adults in the Golestan province (north of Iran) in 2006.Methods: This is a Cross-sectional–Descriptive and population-based study, carried out among 1999 cases (1000 men and 999 women) between 25 and 65years old. Participants were chosen by cluster and stratified sampling in urban and rural areas. Data on socio-demographic factors were collected using questionnaire, and anthropometric and biochemical indexes were measured. Fasting Blood Sugar (FBS) equal to or over 126mg/dl was classified as type 2 DM.Results: Mean of age was 39.2years and mean±SD of FBS among men and women was 94.51±32.91 and 98.2±40.1mg/dl, respectively. Prevalence of DM was 8.3% [(men=6.8% and women=9.7%), (urban=10.5% and villages=6.4%)]. Twenty-five percent of patients were undiagnosed as whole, 43% of patients were unaware of their problem, in men more than in women (48.5% versus 39.2%) and in rural area more than in urban area (35.1% versus 54.4%). We showed a positive and significant correlation between FBS and age, waist circumference and BMI (P=0.01).Conclusion: DM was the one of the biggest health problems in the north of Iran, and half of them were unaware of their morbidity. DM was influenced by socio-demographic factors.

A new paradigm between mechanical scaling and root planing combined with adjunctive chemotherapy for glycated hemoglobin improvement in diabetics

2010-10-08

Abstract: Aim: The objective of the study was to evaluate the effectiveness of scaling and root planing (SRP) and adjunctive chemotherapy (doxycycline hyclate, 20mg) on gingival health, specific cytokines and glycemic control in diabetic subjects.Methods: Three hundred and forty-six type 1 and 2 diabetic subjects were randomized into four test groups: (1) one session of SRP at the baseline visit and placebo tablets twice/day, started at the baseline visit, for 3months, (2) one session of SRP at the baseline visit, and doxycycline hyclate (20mg, twice/day) started at the baseline visit for 3months, (3) two sessions of SRP, first at the baseline visit and second at the 6months, with placebo tablets twice/day started at the baseline visit and 6-month visit, for 3months at each visit, and (4) two sessions of SRP, first at the baseline visit and the second at the 6-month visit, and doxycycline hyclate 20mg twice/day, started at the baseline visit and the 6-month visit, for 3months at each visit. Venous blood samples were obtained to evaluate TNF-α, IL-1α and glycated hemoglobin (HbA1c); dental measurements were also included.Results: HbA1c showed significant improvement (P<0.05) only for subjects with glycated hemoglobin ⩽8.8% within each group, as well as when subjects were combined together. All groups achieved statistically significant improvements for most of the dental parameters at follow-up visits (P<0.05) compared to the baseline.Conclusions: Eliminating periodontal inflammation may significantly reduce glycated hemoglobin levels for subjects with HbA1c ⩽8.8%; furthermore, SRP and adjunctive therapy improved periodontal inflammation in diabetics.

Association of serum TNF-α and IL-6 with insulin secretion and insulin resistance in IFG and IGT subjects in a Bangladeshi population

2010-10-01

Abstract: Background: TNF-α and IL-6 have been shown to be associated with insulin resistance in T2 DM subjects. However, their causal role in the development of diabetes is still unsettled.Subjects and methods: In the present study 106 prediabetic subjects (17 IFG, 60 IGT, 29 IFG-IGT) were studied along with age- and BMI-matched 56 healthy controls. Insulin was measured by ELISA; TNF-α and IL-6 were measured by chemiluminescence-based EIA.Results: Fasting serum TNF-α and fasting serum IL-6 levels were not significantly different among the groups. However, a significant association of TNF-α (p<0.013) with prediabetic (IGR) state on binary logistic regression analysis was shown when the effects of sex, BMI, WHR, HOMA B and HOMA S were adjusted. On multinomial logistic regression analysis a significant positive association of TNF-α was observed with IGT and IFG-IGT subjects (p=0.008, p=0.008) when the effects of sex, BMI, WHR, HOMA B and HOMA S were adjusted. On multiple linear regression analysis TNF-α showed a significant positive association with insulin secretory capacity when adjusting the effects of the confounding factors.Conclusions: TNF-α is positively associated with IGT and IFG-IGT state and may have a causal relation with insulin secretory defect in IGR or prediabetic subjects.

High glucose-induced DNA-binding activities of nuclear factor of activated T cells 5 and carbohydrate response element binding protein to the myo-inositol oxygenase gene are inhibited by sorbinil in peripheral blood mononuclear cells from patients with type 1 diabetes mellitus and nephropathy

Bingmei Yang, Andrea Hodgkinson, Beverley A. Millward, Andrew G. Demaine — 2010-10-04

Abstract: Aims: To investigate whether high glucose induces myo-inositol oxygenase (MIOX) expression in peripheral blood mononuclear cells through transcription factors, nuclear factor of activated T cells 5 (NFAT5) and carbohydrate response element binding protein (ChREBP), which may contribute to the pathogenesis of diabetic nephropathy.Methods: 34 patients with type 1 diabetes mellitus (20 with nephropathy, 14 without complications) and 9 healthy controls were recruited in this study. Peripheral blood mononuclear cells were exposed to normal, high glucose conditions with/without an aldose reductase inhibitor (ARI), using electrophoretic mobility shift assays the DNA-binding activities of NFAT5 and ChREBP to corresponding sites in the promoter region of MIOX gene were analysed. The protein levels and the enzyme activity of MIOX were measured.Results: DNA-binding activities of NFAT5 and ChREBP were increased under high glucose conditions and decreased in the presence of the ARI in all groups. In the presence of ARI, the DNA-binding activities of NFAT5 and ChREBP were significantly decreased by 41% (NFAT5: 0.91±0.06 vs. 1.54±0.12; p=0.01) and 49% (ChREBP: 0.92±0.08 vs. 1.81±0.22; p=0.001) compared with high glucose in patients with nephropathy. ARI treatment decreased the protein levels of MIOX under high glucose conditions in patients with nephropathy (0.81+0.19 vs. 1.3+0.04; p=0.049).Summary/conclusions: There was a trend for increased binding activities of NFAT5 and ChREBP accompanied with increased protein levels under high glucose, particularly in patients with nephropathy. ARI treatment prevented these increases and this effect was more obvious in the patients with nephropathy compared to the uncomplicated subjects.

Early metabolic imprinting as a determinant of childhood obesity

C. Scerri, C. Savona-Ventura — 2010-10-06

Abstract: Aims: Childhood obesity has seen an alarming increase in recent decades. This study was designed to assess the role of family history and perinatal programming in the aetiology of childhood obesity in a population known to have a high risk of developing metabolic syndrome.Methodology: The study was carried out among two study populations of children. The first was a population of 206 mixed-gender 5-year-old children; the second of 230 mixed-gender 9-year-old children. The children underwent standard anthropomorphic measurements that were correlated to family history of metabolic syndrome-related illness, the child’s birth weight and a history of breastfeeding in early infant life.Results: No statistically significant correlation was noted with a family history of metabolic syndrome; but a definite (P=0.04) negative correlation was noted with breastfeeding in the 5-year-old children. Children of low birth weight appeared to retain a lower body weight at five years of age than their higher birth weight counterparts (P=0.002). The pattern changed to suggest a U-shaped distribution of obesity among the various birth weight groups of children, though statistical significance was noted only for the macrosomic group (P=0.002).Conclusions: The study confirms the importance of intrauterine and early infant nutrition towards the development of childhood and later obesity. Children of low or high birth weight should be considered at risk and parents are advised actively regarding health lifestyle and nutrition options.

Association of CD36 gene variants rs1761667 (G>A) and rs1527483 (C>T) with Type 2 diabetes in North Indian population

2010-10-08

Abstract: Introduction: Type 2 diabetes mellitus (T2DM) affects huge populations in India and abroad. Genetic polymorphisms (SNPs) in scavenger receptors such as CD36 have been implicated in the pathogenesis of diabetic atherosclerosis and cardiovascular diseases. Since CD36 gene expression contributes to T2DM, we proposed to study the association of two of its polymorphisms.Methods: A population of 400 subjects from North India was analyzed according to clinical parameters. Out of them 150 controls and 250 T2DM patients were genotyped for two SNPs namely rs1761667 (G>A) and rs1527483 (C>T) in the CD36 gene using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) followed by statistical analysis.Results and discussion: No association of rs1527483 (C>T) SNP was observed in T2DM patients. The GA genotype was prevalent in 76.0% diabetic population and a highly significant genotypic association of rs1761667 (G>A) SNP in CD36 gene was observed in them (P=<0.001; OR 3.173; CI 1.098–9.174). Sample characteristics showed a highly significant association with lipid profile (P=<0.001). The ‘GA’ genotype in combination with CC genotype showed a significant association with TC (P=0.020), LDL (P=0.005) and VLDL (P=0.029). In addition, the haplotype analysis CC/GA (−/+) and CT/GA (−/+) showed a strong association with TC and LDL (P<0.05). The presence of −31118A∗ allele in haplotypes showed strong association with T2DM (P=<0.005).Conclusion: Out of the two CD36 gene polymorphisms tested, rs1761667 SNP is significantly associated with T2DM with the GA heterozygous genotype showing highest frequency among the T2DM patients.

Current clinical status and complications among type 2 diabetic patients in Universiti Sains Malaysia hospital

2010-09-28

Abstract: Objective: To identify current clinical status of type 2 diabetic outpatients and to determine the prevalence of diabetic complications and risk factors.Material and method: Prospective cross-sectional study design was used in the data collection process. The study sample consists of 1077 type 2 Diabetes Mellitus outpatients who fit the inclusion criteria. All the patients were recruited from the diabetic outpatient clinics from Hospital Universiti Sains Malaysia (HUSM). The study period was from January till December 2007. Demographic data, clinical status of diabetes and its complications were collected and analyzed for the prevalence of complications and risk factors.Results: One thousand and seventy seven type 2 diabetes outpatients were included in the present study. Mean age was 58.3years and duration of diabetes was 11years. Only 23.4% of the subjects achieved HbA1c of ⩽7%, 53.5% of patients had achieved target FPG ⩽6.7mmol/l, and 60.4% of the patients had achieved optimal postprandial plasma glucose level <10mmol/l. The overall prevalence of dyslipidaemia was 93.7%, hypertension was 92.7% and obesity was 81.5%. Nephropathy was the most common complication accounting for 91.0% followed by neuropathy 54.4%, retinopathy 39.3%, and macrovascular complications 17.5%. The vascular complications were significantly associated with the age (P<0.001), BMI (P<0.001), and triglyceride (P<0.001).Conclusion: The prevalence of dyslipidaemia, hypertension and obesity were high. The high prevalence of vascular complications was associated with age, BMI and triglyceride of diabetic patients. Effort to treat triglyceride appropriately among elderly diabetic patients could be considered as a prime target.

Endothelial cell dysfunction in hyperglycemia: Phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes

Doina Popov — 2010-10-08

Abstract: Hyperglycemia, the hallmark of Diabetes mellitus, is a major risk factor for endothelial dysfunction and vascular complication. In recent years, significant achievements have been made in understanding endothelial cell dysfunction triggered by high glucose concentration. The purpose of this review is to discuss the results of these recent developments. First, the remarkable plasticity of vascular endothelial cell in response to the high glucose insult is emphasized. This is evident through the switch in the cell’s normal quiescent profile into new phenotypes, endowed with biosynthetic, inflammatory, adhesive, proliferative, migratory, pro-atherogenic, and pro-coagulant properties, frequently overlapping each other. Then, we underline the imbalanced expression and activity of transcription and signaling pathways, and the intense metabolic activity that accompanies the change in endothelial cell phenotype. As an adaptation to the high glucose-induced biochemical modification, a severe alteration of cell structure is produced. The review concludes with the clinical outcomes of the subject, emphasizing the high glucose-associated endothelial cell dysfunctional molecules of potential for targeting, and for reducing the impact of hyperglycemia on vascular endothelium. Such interventions may lead to a more efficient therapy for the benefit of those diabetic patients who are at increased cardiovascular risk.

Spontaneous gas gangrene of the scrotum in patient with severe diabetic ketoacidosis

2010-10-29

Abstract: A 52-year-old Chinese man presented with severe diabetic ketoacidosis and markedly inflated scrotum. Computed tomographic scans of the lower pelvis show extensive gas accumulation and inflammatory changes in both sides of the scrotum. Gas gangrene of the scrotum was diagnosed and radical debridement along with other proactive anti-ketoacidosis therapy was performed immediately. Clostridium perfringens was found in cultures of necrotic tissue that verified the diagnosis and the patient was cured through multiple proactive treatments.