Mitochondrial disorder, diabetes mellitus, and findings in three muscles, including the heart

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.     

Mitochondrial Disorder,Diabetes Mellitus,and Findings in Three Muscles,Including the Heart

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.     

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

We present an autopsy report on a 14-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), placing emphasis on the mitochondrial enzymatic histochemistry of the 3 types skeletal muscle and cardiomyocytes. Generalized muscular atrophy, cardiac hypertrophy, cerebral cortical laminar necrosis, basal ganglia calcification and liver steatosis were observed. In the skeletal muscles, modified Gomori's trichrome staining demonstrated scattered ragged red fibers, and histochemical staining for mitochondrial enzymes showed intense positivity in the subsarcolemmai zones of some muscle fibers. Some of the hypertrophic cardiomyocytes also showed a ragged red appearance with the modified Gomori's trichrome stain. Histochemical staining for mitochondrial enzymes showed patchy loss of enzymatic activity in the myocardium. Electron microscopically, extreme accumulation of enlarged mitochondria and severe loss of myofibrils was observed in both skeletal muscle fibers and cardiomyocytes. The arteriolar smooth muscle cells also showed a mild increase in mitochondria. Acta Pathol Jpn 39: 599 606, 1989.     

Synergistic effects of diabetes mellitus and renovascular hypertension on the rat heart - stereological investigations on papillary muscles

Summary The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive nondiabetic young male Wistar rats were compared with diabetic and nondiabetic controls. Since the normal body weight increase of the diabetic animals was markedly suppressed a weight-matched nondiabetic control group was introduced in addition. Hypertension was established for eight weeks by a surgical stenosis of the left renal artery, diabetes mellitus was maintained for four weeks after a single intraperitoneal injection of 75 mg/kg streptozotocin. Light and electron microscopic stereological parameters were obtained for the left ventricular papillary muscles. The whole hearts were also investigated histologically. Qualitative morphology failed to substantiate synergistic effects in the hypertensive diabetic rats. Vascular abnormalities were not observed. The stereological parameters, however, revealed microstructural reactions which were observed exclusively in the hypertensive diabetic group: the volume ratio of mitochondria-to-myofibrils was decreased, the surface-to-volume ratio of mitochondria was increased (reduction of mitochondrial size) and the mean cross sectional area of capillaries was decreased. Similar quantitative mitochondrial changes have been frequently described in long-standing hypertension, but in the present investigation, they were not found in the nondiabetic hypertensive group. It is therefore concluded that diabetes mellitus potentiates the effects of chronic pressure overload on myocardial cells. However, the myocardial fibrosis which has been found by other groups at later stages of hypertension and/or diabetes mellitus was not detected in the present study. The reduced mean cross sectional area of capillaries in hypertensive-diabetic rats may be correlated with early molecular changes of the myocardial interstitium or with early abnormalities of small arteries. Thus our stereological results support the hypothesis that a non-coronary hypertensive diabetic cardiomyopathy occurs in mammalian hearts.The results were presented in part at the Erwin Riesch Symposium,The results were presented in part at the Erwin Riesch Symposium,Dedicated to Prof. Dr. Drs.h.c.mult. G. Schettler on theDedicated to Prof. Dr. Drs.h.c.mult. G. Schettler on the     

Clinicopathological findings of diabetes mellitus induced by alloxan in goats

Alloxan is used for treatment of insulinoma in humans and to induce experimental diabetes in animals. The objective of this research was to study the clinicopathological abnormalities induced by alloxan in goats and to evaluate induced diabetes mellitus disease in goats. Eight goats were divided into treatment (n=4) and control (n=4) groups. After intravenous glucose tolerance tests (IVGTT), goats in the treatment group were injected with 80 mg/kg BW alloxan monohydrate intravenously. Clinical findings in the treatment group included hyperglycemia, glycosuria, ketonemia, ketonuria, polyuria, polydipsia, polyphagia, depression, and pulmonary and dermal infections during the study period. Hematological investigations in the treated goats showed a significant decrease in RBC, Hb, PCV, and lymphocytes (p<0.05) and a significant decrease in neutrophil count (p<0.05). Biochemical investigations in the treatment group indicated a significant increase in glucose, BUN, triglyceride, and total protein levels (p<0.05) but a significant decrease in cholesterol (p<0.05). Urinalysis showed the presence of glucose, ketone bodies, protein, leukocyte, and blood in the urine of the treated goats as well as a decrease in pH.     

Kidney biopsy findings in cyclosporine-treated patients with insulin-dependent diabetes mellitus

Summary Renal biopsy specimens of 40 patients with recent-onset insulin-dependent diabetes mellitus treated with cyclosporine (CSA) for 6–29 months were examined. Cyclosporine-associated chronic vascular interstitial toxicity of moderate intensity was found in 10 patients (25%). The most prominent lesions were interstitial fibrosis and tubular atrophy. Arteriolopathy was less pronounced and glomerular damage unremarkable.A significant correlation exists between the extent of tubular atrophy and CSA trough whole blood levels.These data indicate that the development of CSA-associated chronic nephropathy is dose-dependent.     

2型糖尿病患者线粒体基因8个突变位点的研究

目的：探讨线粒体DNA tRNA Leu (UUR)基因及其相邻的ND1基因8个位点的突变与2型糖尿病的关系。 方法： 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的分析方法，对174例2型糖尿病患者和207名健康对照的mtDNA的3 243、3 256、3 290、3 316、3 394、3 421、3 426、3 460和3 593共9个已报道的突变位点同时进行筛选，并采用测序、反向斑点杂交和基因芯片进行方法学比较和确证，对检出的突变位点采用DNASTAR和Antherprot软件进行分析。 结果： 糖尿病组检出3 316(G→A) 突变5例(2.9%)，其中2例为多个位点突变：1例伴随3 256(C→T)和3 688(G→C)，另1例伴随3 606(A→G)；3 394(T→C)突变4例(2.3%)，3 593(T→C)、3 290(T→C)和3 618(T→C)突变各1例(0.6%)； 其中3 606(A→G)、3 618(T→C)和3 688(G→C) 为新突变位点，GenBank登录号为DQ092356；对照组只检出3 316(G→A)突变1例(0.5%)。两组间仅3 394(T→C) 突变率差异显著(P<0.05)。以上8个突变位点的测序、反向斑点杂交和基因芯片检测结果完全一致。3 606(A→G)为Leu的无意义突变，3 618(T→C)为Phe的无意义突变，3 688(G→C)为有意义突变，Ala→Pro,导致ND1蛋白的二级结构发生改变。 结论： 线粒体DNA ND1基因3 316(G→A)突变伴随3 688(G→C)突变，3 394(T→C) 突变可能与2型糖尿病发病有关。     

Diet selection and metabolic fuels in three models of diabetes mellitus

Dietary self-selection and circulating metabolic fuels (glucose, free fatty acids, ketones) were examined in three forms of experimental diabetes mellitus in rats: pancreatectomy and streptozotocin treatment in adult and neonatal rats. Changes in diet selection resulting from insulin replacement also were examined. Differences were found in diet selection and circulating metabolic fuels between these types of diabetes. Mildly diabetic rats selected large amounts of fat while more severely diabetic rats primarily selected protein. Insulin treatment enhanced carbohydrate intake of diabetic rats and nearly normalized diet selection and circulating metabolic fuels. All diabetic groups exhibited severe glucose intolerance. These results support the observations of the beneficial effects of low-carbohydrate diets, question the generality of the use of high-fat diets, and suggest a more important role for high-protein diets in energy regulation in severely diabetic rats.     

长链非编码RNA与糖尿病关系的研究进展*

Long non-coding RNAs (lncRNAs) are a group of RNAs, which are longer than 200 nucleotides without containing functional open reading frame and cannot encode protein. The study of lncRNA will help to understand the multi-level expression regulatory network of the body, and is expected to provide the basis of prediction, diagnosis and treatment of complex diseases. Although the functions and mechanism of lncRNA remain unclear, some studies indicate that lncRNA is involved in the development of diabetes mellitus, and those lncRNAs may be new diagnostic markers and therapeutic targets.     

糖尿病对精液质量的影响及其机制

糖尿病是由多种病因引起的代谢性疾病,不仅影响男性性功能而且影响男性精液质量。本文综述了糖尿病对男性精液的影响如精子活动力、精子密度、精子DNA损伤等及其发生机制。     

Nodular fibrosis of the lung in diabetes mellitus

The target organs in diabetes mellitus include the kidneys, the eyes and the small vessels. In these organs some specific histopathological changes have been described but there are few reports of histopathoogical changes in the lung in diabetic patients. Several reports describe abnormal pulmonary function in diabetic patients and consider these abnormalities to be due to histopahtological changes found in the pulmonary vessels. We have studied the histopathological changes in the diabetic lung comparing the findings in the autopsies of 61 diabetic and 50 non-diabetic patients. Statistically significant differences in the incidence of chronic obstructive lung disease and pulmonary haemorrhage exist. There are no differences in the incidence of fibrosis of the alveolar walls or intimal and medial thickening of small vessels, changes associated with diabetes according to the literature. We have found a specific type of nodular fibrosis not previously reported which we believe to be typical of diabetes.     

Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus

Summary Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.This work was supported in part by N.I.H. grant DE-03933. We would like to thank Mrs. Valerie Every for her secretarial assistance.     

Plasma catecholamines and renin in diabetes mellitus

Summary Plasma and urinary norepinephrine (PNE, UNE) and epinephrine, plasma renin activity (PRA) and their interrelations with posture, age, the body sodium-volume state and blood pressure were analyzed in 90 normal and 100 non-azotemic diabetic subjects. Ages ranged from 18 to 76 yrs, urinary sodium from 51 to 249 mEq/24h. Fortysix patients had a normal supine blood pressure, 54 had hypertension. Diabetics had an increased (p<0.01) mean exchangeable sodium, while blood volume was normal. Upright posture caused a comparable increase in PNE in normal and diabetic subjects; but the response of PRA was blunted (p<0.001) in diabetics, with subnormal responsiveness in 32% of cases. Epinephrine levels in diabetics were normal and unchanged with posture or age. In both groups supine and upright PNE and PRA correlated (p<0.05) positively with age, but not with urinary sodium. Comparison with dynamic normal ranges relative to age revealed low upright PNE in 14% and low or high PRA in 12 and 6% of diabetics, respectively. The low-norepinephrine subgroup had a higher exchangeable sodium and lower PRA than the normal-norepinephrine patients (p<0.025). Low-renin patients had a higher exchangeable sodium and lower UNE than normal or high-renin patients. Orthostatic decrease in blood pressure was noted in low or normal-renin, but not in high-renin patients. These findings suggest that patients with non-azotemic diabetes mellitus have usually a normal adrenergic response to postural changes; and physiological variations of PNE and PRA with age are largely maintained. However, diminished renin-responsiveness is common. Distinct sodium retention could contribute to norepinephrine or renin suppression in some patients and possibly also to the frequent development of hypertension in diabetes mellitus.This work was supported by the Swiss National Science Foundation     

Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder,major depressive disorder,and schizophrenia: A 10-year nationwide population-based prospective cohort study

Background

The high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study.

Method

Using a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia.

Results

The identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3±14.0, 46.5±13.7, and 45.9±12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155–2.507) and schizophrenia (HR of1.793, 95% CI: 1.532–2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107–2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002–1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls.

Conclusions

This first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.     

瘦素、抵抗素、2型糖尿病间的相关性研究

目的：研究血浆瘦素与抵抗素、体重指数、腰围、腰臀比、血脂、胰岛素敏感性指数等的关系。方法：对43例新诊断2型糖尿病患者及37例糖耐量正常者，测定空腹血浆瘦素、胰岛素、血糖、血脂及抵抗素浓度。结果：相关分析显示性别、体重指数（BMI）、腰围、腰臀比、胰岛素与瘦素呈显著正相关（r分别为0.623,0.534，0.516，0.302，0.354，均P<0.01），IAI与瘦素呈显著负相关(r=-0.373,P<0.01),甘油三酯、胆固醇空腹血糖与瘦素无明显相关。瘦素与抵抗素无相关性（r=0.101,P>0.05）结论：空腹血浆瘦素水平与肥胖程度、胰岛素抵抗呈显著正相关，与抵抗素无关。瘦素可能与2型糖尿病的发病有关。     

Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.     

Adrenergic mechanisms and blood pressure regulation in diabetes mellitus

Summary Changes in blood pressure (BP) and plasma norepinephrine (NE) following various stimuli of the sympathetic nervous system were studied in six healthy subjects and in 17 diabetic patients. The latter were subdivided in three groups: (1) six patients with neither peripheral neuropathy nor autonomic dysregulation, (2) six patients with severe peripheral neuropathy without autonomic dysregulation, and (3) five patients with autonomic dysregulation, three of whom suffered also from peripheral neuropathy. The following procedures were performed: (1) cold pressor test (2 min), (2) mechanical irritation of the skin by suction (0.75 kg/cm², 10 min), (3) orthostasis (10 min), and (4) i.v. infusion of NE (50, 100, 200 ng kg^–1 min^–1 for 15 min each). Both the stimulated endogenous plasma NE levels and BP response to exogenous NE were the same in normal subjects, in diabetic controls and in diabetics with peripheral neuropathy without autonomic dysregulation. In contrast, diabetics with postural hypotension showed a less pronounced release of NE to standing (P<0.05), but not to cold pressor test and mechanical skin irritation. Furthermore, they showed increased vasoreactivity to the highest dose (P<0.05), but not to the lower doses of exogenous NE. Thus NE release and adrenergic BP regulation seem to be altered only in diabetics with clinical signs of autonomic dysregulation. These alterations can only be evaluated when patients are exposed to stimuli of higher intensity, such as orthostasis or infusion of a high NE dose.     

瘦素、脂联素、抵抗素、内肥素与妊娠糖尿病胰岛素抵抗的相关性研究

目的:探讨脂肪因子瘦素、脂联素、抵抗素、内肥素与妊娠糖尿病(GDM)胰岛素抵抗的相关性.方法:实验分为正常育龄妇女组(44例)、正常妊娠妇女组(62例)和妊娠糖尿病患者组(63例),用ELISA方法分别检测3组瘦素(Leptin),脂联素(Adiponectin),抵抗素(Resistin),内肥素(Visfatin)的水平,用葡萄糖氧化酶法检测血糖水平,免疫发光法检测胰岛素水平,用HOMA-IR(稳态模型胰岛素抵抗指数)表示胰岛素抵抗状态,HOMA-IR=空腹血糖×空腹血胰岛素÷22.5,用SPSSll.5统计软件进行统计分析.结果:妊娠糖尿病患者组的瘦素水平明显高于正常妊娠妇女组[(13.50±7.14)ng/ml、(7.78±3.82)ng/ml,P<0.001],正常妊娠妇女组明显高于正常育龄妇女组[(7.78±3.82)ng/ml、(1.73±0.70)ng/ml,P<0.001]差异具有统计学意义;GDM 组的内肥素水平明显低于正常妊娠妇女组[(15.67±5.78)ng/ml、(22.43±5.68)ng/ml,P<0.001],正常妊娠妇女组明显低于正常育龄妇女组[(22.43±5.68)ng/ml、(36.46±13.34)ng/ml,P<0.001],差异具有统计学意义;GDM 组的脂联素水平低于正常妊娠妇女组[(5 491.71±2 986.00)ns/ml、(6 692.34±2 583.51)ng/ml,P=O.029],差异有统计学意义,正常妊娠妇女组明显低于正常育龄妇女组[(6 692.34±2 583.51)ng/ml、(11 076.82±3 694.75)ng/ml,P<0.1301],差异具有统计学意义;GDM组抵抗素水平与正常妊娠妇女组比较差异没有统计学意义.在妊娠糖尿病患者组,HOMA-IR与瘦素(r=0.352,P=0.005)正相关,与内肥素(,=-0.255,P=0.046)呈负相关.结论:妊娠糖尿病患者瘦素水平升高,内肥素和脂联素水平降低,瘦素和内肥素与胰岛素抵抗有关,瘦素和内肥素参与了妊娠糖尿病胰岛素抵抗的发生发展;脂联素和抵抗素与胰岛素抵抗不具有相关性,脂联素和抵抗素可能与妊娠糖尿病胰岛素抵抗的发生无关.     

The cutaneous silent period in diabetes mellitus

The cutaneous silent period (CSP) may be useful as a method for the evaluation of smaller and unmyelinated fiber dysfunctions. CSP refers to the brief interruption in voluntary contraction that follows strong electrical stimulation of a cutaneous nerve. The aim the present study is to establish whether CSP can be instrumental in the determination of diabetic neuropathy. The nerve conduction studies and CSP evaluations were both used in patients with Diabetes Mellitus and control group. All patients were given clinical neurological examinations for the determination of small-fiber neuropathy (SFN). The CSP values for patients with SFN were compared with values of those without SFN. The nerve conduction velocities had changed unfavorably in diabetic patients. No median nerve CSP reponse could be obtained in two of the diabetic patients. CSP latency (84.6+/-14.0) in diabetics was longer than controls (76.2+/-13.1) (p=0.018). The duration of CSP was similar for the two groups (p=0.46). The CSP latency showed a correlation with routine nerve conduction studies. While the CSP latencies (86.7+/-15.8) of patients who were clinically diagnosed with SFN were similar to the latencies (81.3+/-10.4) of patients without SFN (p=0.606), the duration of CSP (44.6+/-13.7) in patients with SFN was shorter than the duration (55.3+/-12.2) in patients without SFN (p=0.012). These results indicate that even though the CSP does not provide any advantage over routine electrodiagnostic studies in determining diabetic neuropathy, still it may be a useful method for the early detection of diabetic SFN.     

Mitochondrial gene mutations in familial non-insulin-dependent diabetes mellitus in Taiwan

Mitochondrial gene mutations are found to cause certain forms of diabetes mellitus and related syndromes. To study the prevalence of mitochondrial gene mutations in subjects with non-insulin-dependent diabetes mellitus (NIDDM) in Taiwan, 23 pedigrees with multiple siblings affected with NIDDM were consecutively collected from patients living in northern Taiwan. The A-to-G mutation at position 3243 np in the tRNALeu gene and the mutation at position 8344 were screened by PCR-RFLP methods and confirmed by direct DNA sequence analysis. Among 23 NIDDM pedigrees, one pedigree was found to carry the 3243 np mutation. There was no 8344 np mutation in this series. Clinical features of this pedigree were consistent with mitochondrial disease in terms of maternal transmission, relatively early onset, non-obesity, insulin-requirement and association with hearing impairment. There was no correlation between the degree of heteroplasmy of mitochondrial gene mutation in leukocyte DNA and clinical severity. We conclude that a mitochondrial gene defect is an important genetic factor in familial cases with NIDDM in Taiwan.