Non-obese Diabetes Mellitus Research Articles

Clinical characteristics and efficacy of pioglitazone in a Japanese patient with familial partial lipodystrophy due to peroxisome proliferator-activated receptor γ gene mutation.

Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 μg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.

The ambulatory blood pressure monitoring among obese and nonobese diabetes mellitus patients.

Obesity and diabetes mellitus are two major factors related with the risk of metabolic syndrome and cardiovascular diseases. Co-existing hypertension with diabetes mellitus and obesity has poor prognosis for cardiovascular diseases. Ambulatory blood pressure monitoring (ABPM) correlates more closely to target organ damage than clinic blood pressure. The objective of the study is to assess and compare ABPM pattern among obese and nonobese diabetes mellitus patients. A cross-sectional study was conducted among fifty obese and fifty nonobese diabetic patients who were classified based on their body mass index as per the WHO criterion. The clinical blood pressure measurements were measured on each subject using a digital sphygmomanometer, and 24 h ABPM was done and ABPM parameters such as dipping pattern, 24 h systolic blood pressure (SBP), diastolic blood pressure (DBP), Mean SBP, mean DBP, diurnal variability of SBP, DBP, Mean arterial pressure, pulse pressure, SD systole (Standard Deviation systole), SD diastole, white coat hypertension was derived and compared between the two groups. Around 37 (74%) obese and 18 (36%) nonobese showed non dipping pattern in SBP and 28 (66.7%) of obese and 14 (33.3%) of nonobese showed a nondipping pattern in DBP and was found to be statistically significant (P < 0.001). On comparison between normotensive obese and normotensive nonobese, it was found that SBP non dipping pattern18 (67%) versus 9 (29%) and DBP nondipping pattern 12 (45%) versus 5 (16%) was statistically significant with P = 0.004, 0.016, respectively. Obese diabetes mellitus subjects had altered ABPM parameters and increased prevalence of nondipping status. In addition, obese diabetic patients who did not give prior history of hypertension were also found to have higher nondipping SBP and DBP patterns.

Sleeve gastrectomy and pancreas omentoplasty improved β cell insulin expression and interleukin-1β serum level in non-obese diabetes mellitus rat

Background: Diabetes mellitus is one of the health problems that is growing rapidly today. In Asia, majority of the population are non-obese with Type 2 Diabetes Mellitus (T2DM). Two main defects of T2DM, insulin resistance and impaired insulin secretion due to reduced pancreatic β cells. Persistent metabolic stress due to hyperglycemic conditions, causes inflammation of the islets of Langerhans. Interleukin-1β (IL-1β) signaling is the most frequent pathway inducing β cell dysfunction. The bariatric Sleeve Gastrectomy (SG) procedure increases particular hormone which stimulates β cell growth and pancreatic insulin production. Aside from the role as a blood glucose regulator, insulin also plays a role in anti-inflammatory modulation. Omentoplasty can be used to wrap organ or tissue structures. The Omentum has unique biological functions, including promote tissue regeneration and anti-inflammatory effect. The study evaluates the effect of Sleeve Gastrectomy and pancreas Omentoplasty procedures on β cell insulin expression and Interleukin-1β (IL-1β) serum levels in non-obese diabetes mellitus subjects.Methods: Experimental study with "post-test control group design" on 27 rats with Diabetes Mellitus was divided into 3 groups: K (control), P1 (Sleeve Gastrectomy), P2 (Sleeve Gastrectomy + Omentoplasty). 10 days after procedure, we evaluated the insulin expression of β cells using monoclonal antibody anti-insulin stain and IL-1β serum levels using rat IL-1β Enzyme-Linked Immunosorbent Assay (ELISA) kit. Statistical analysis with Kruskal Wallis and Mann Whitney test. Correlation test with Spearman.Results: β cell insulin expression increased in P2 (p=0.020), compared to control. While the IL-1β serum levels reduced significantly in all groups (p<0.001) compared to control. Moderate negative correlation (r = -0.476) between β cell insulin expression and IL-1β serum levels.Conclusion: Sleeve gastrectomy and omentoplasty increased β cell insulin expression and decreased IL-1 β serum levels in non-obese rats with diabetes mellitus.

Maternally Inherited Diabetes and Deafness in a North American Kindred: Tips for Making the Diagnosis and Review of Unique Management Issues

Mutations in mitochondrial DNA are rare etiologies of adult-onset diabetes mellitus (DM) that merit identification to 1) prevent iatrogenic lactic acidosis, 2) prompt appropriate screening of affected patients and their families, 3) provide genetic counseling, and 4) provide an opportunity to investigate strategies for preventing diabetes. The objective of this study is to raise awareness of this rare form of adult-onset nonobese DM so that these patients are identified and provided with appropriate care. We describe a kindred in which four of seven siblings have adult-onset DM and sensorineural hearing loss with a confirmed genetic mutation at position 3243 in the tRNA. Two other siblings in this kindred demonstrate different phenotypes of mitochondrial disease. The proband was treated with coenzyme Q10 for 1 yr. Outcome measures included stress thallium exercise testing and audiometry testing. After 1 yr of treatment of with coenzyme Q10, repeat stress thallium testing demonstrated improvement in the exercise tolerance of the proband from 7-12 min. Audiometry testing did not demonstrate a change in the rate of hearing decline. Maternally inherited diabetes and deafness is a rare cause of DM that is important to diagnose because of the unique management issues and associated comorbidities. This work highlights clues to the identification of this rare monogenic form of adult- onset diabetes.

Molecular Genetic Analysis of MODY Candidate Genes in Japanese Patients with Non-Obese Juvenile Onset Diabetes Mellitus

We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF-4alpha and HNF-1beta. In HNF-1alpha, previously reported mutations (R271W and R272C) and one novel sequence variant (at nucleotide -129/-130 insTTGGGG of the promoter region) were identified in three different patients. In vitro functional study of the new promoter variant demonstrated that the transcriptional activity was 1.6-2.0 times higher than that of the wild-type. This may lead to overexpression of HNF-1alpha and subsequent negative regulation of the target genes of HNF-1alpha. No mutation was identified in the HNF-4alpha and HNF-1beta genes. In this study on a small series of non-obese Japanese patients with juvenile-onset DM, the prevalence of MODY3 was 3.5%. The significance of the new promoter variant in the development of DM is unclear; however, a promoter mutation in the HNF-1alpha gene could be diabetogenic.

Low‐dose metformin improves hyperglycaemia related to myotonic dystrophy

One of the clinical features of myotonic dystrophy is insulin resistance with non-obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity. A 58-year-old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA(1c) 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA(1c) was decreased to 7.4%, while HOMA-IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA(1c) was maintained (7.5%). It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin-independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients.

Insulin Resistance Is Associated with Increased Circulating Level of Thrombin-Activatable Fibrinolysis Inhibitor in Type 2 Diabetic Patients

Hypofibrinolysis is a common finding in patients with diabetes mellitus (DM) and obesity and a risk factor for the development of cardiovascular disease. Recently, a new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. The present study was undertaken to assess the activity and circulating level of TAFI and its relation to fibrinolytic function and obesity in patients with type 2 DM. Fifty-seven patients with type 2 DM (38 men, 19 women) were enrolled in this study. DM patients were categorized in age-matched obese [body mass index (BMI) > or = 25] and nonobese (BMI < 25) groups. The plasma concentration and activity of TAFI were significantly (P < 0.05) higher in DM patients than in healthy controls. The plasma levels and activity of TAFI were significantly (P < 0.05) elevated in obese DM patients compared with nonobese DM and nonobese healthy subjects. RT-PCR demonstrated the expression of TAFI in human adipose tissue and in human endothelial cells. The plasma levels of TAFI were independently and significantly correlated with glucose intolerance (HbA(1c)), with obesity (BMI, visceral fat area), and with an indicator of insulin resistance (glucose infusion rate). This study showed that increased circulating level of TAFI may be an important causative factor of hypofibrinolysis in patients with type 2 diabetes, obesity and insulin resistance.