Volume 09 · Issue 06 · 2017

Adult-onset diabetes mellitus (MODY) in adolescents is the most common type of monogenic diabetes, accounting for 2% to 5% of diabetes mellitus^[1]。 Its clinical characteristics include: (1) family history of three consecutive generations or more, with autosomal dominant inheritance; (2) Age of onset of at least one person in the family<Age 25; (3) Not dependent on insulin therapy for at least 5 years, no ketosis predisposition^[2]。 MODY has strong clinical heterogeneity. Due to the large overlap between its clinical manifestations and type 1 diabetes (T1DM) and type 2 diabetes (T2DM), about 80% of MODY are currently misdiagnosed as T1DM or T2DM, resulting in a great underestimation of its actual prevalence^[3]。 Misdiagnosis not only delays the disease, aggravates the progression of diabetes, but also increases the economic burden of families and society. Therefore, it is particularly important to identify MODY from T1DM and T2DM, correctly diagnose and give appropriate treatment in time, evaluate its complications, prognosis, analyze and genetic counseling of patients' family members, and carry out individualized diagnosis and treatment.

In 1999, WHO divided special types of diabetes into eight categories according to etiology. Mitochondrial gene mutation diabetes belongs to the first category, namely "gene defects of pancreatic islet β cell function". Among the special types of diabetes that are clearly caused by gene mutations, mitochondrial diabetes, although the incidence rate is not high, is the most common type. It is not as rare as adult-onset diabetes (MODY) and type A insulin resistance in adolescents. Moreover, the racial differences are small and easier to diagnose. This article summarizes the clinical manifestations, diagnosis and treatment of mitochondrial diabetes, and hopes that clinicians can have a comprehensive understanding of the disease after reading it, and can form a standardized diagnosis and treatment plan in their daily work.

Adult-onset diabetes mellitus (MODY) in adolescents is a special type of diabetes mellitus caused by mutations in a single gene. It is characterized by early onset age, autosomal dominant inheritance, β cell function defects, and no relevant evidence of autoimmunity or insulin resistance^[1]。 At present, 13 types of MODY pathogenic genes have been found, among which MODY3 type [hepatocyte nuclear factor 1A (HNF1 α) mutation], MODY2 type [glucokinase (GCK) mutation] and MODY1 type [hepatocyte nuclear factor 4 α (HNF4 α) mutation] are the most common. Incretin is an intestinal peptide hormone secreted by the gastrointestinal tract, mainly including glucose-dependent insulin-stimulating polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Incretin can promote insulin secretion and inhibit glucagon secretion. In recent years, incretin-based therapy, including GLP-1 receptor agonists and dipeptidyl peptidase IV (DPP-4) inhibitors, has provided more clinical options. This article intends to summarize the recent research related to incretin in MODY and discuss its potential in the treatment of MODY.

To elucidate the clinical characteristics and genotype-phenotype relationships of Chinese patients with neonatal diabetes mellitus (NDM) caused by ATP-sensitive potassium channel (K_ATP) gene mutations (K_ATP-NDM).

Total of 23 suspected patients with NDM were recruited from Peking Union Medical College Hospital. Amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 gene were done for molecular genetic diagnosis. Patients with a definite diagnosis of K_ATP-NDM were switched from insulin injection to oral glibenclamide.

Thirteen patients with K_ATP-NDM were identified, including 9 cases of KCNJ11-NDM and 4 cases of ABCC8-NDM. Four novel mutations of K_ATP were identified: 1 in KCNJ11 (I182M) and 3 in ABCC8 (Q211R,I585F, R653W). Among 9 patients with KCNJ11-NDM, 2 were transient NDM (TNDM) and 7 were permanent NDM (PNDM), and 3 of which had intermediate developmental delay, neonatal diabetes (iDEND syndrome). Four patients with ABCC8-NDM were all PNDM, 2 of them had iDEND syndrome. Switching from insulin to glibenclamide monotherapy was successful in 9 patients (69.2%).

Different clinical severities and treatment responses to sulfonylureas exist even among patients with the same mutation or with different amino acids at the same mutation site. Early diagnosis of K_ATP-NDM and initiation of sulfonylureas are of great importance in the prevention of neurological abnormalities in patients with iDEND syndrome.

To observe the effects of bariatric surgery and the status of food addiction on obese patients with type 2 diabetes mellitus (T2DM) .

A total of 76 obese T2DM patients who had undergone bariatric surgery (operation group, n=38) or traditional medical treatment (control group, n=38) were enrolled from January 2010 to November 2015. The food addiction status was investigated by five core questions of Yale Food Addiction Scale (YFAS) (Q1: eating much more than planned when eating certain foods; Q2: spending time in dealing with negative feelings from consumed certain foods so often or in such large quantities; Q3: consuming the same types or the same amount of food even though having emotional and/or physical problems; Q4: appearance of withdrawal symptoms when cut down or stopped eating certain foods (for example: developing physical symptoms, feeling agitated, or feeling anxious); Q5: behavior with respect to food and eating causes significant distress). Blood glucose, obesity and the food addiction status were investigated. The data of YFAS were analyzed by McNemar test within groups while inter-group comparisons by rank sum test.

Compared with control group, fasting plasma glucose [(5.6±1.0) vs (7.7±2.0)mmol/L], glycated hemoglobin A_1c [(6.1±0.6)% vs (7.3±1.2)%], and body mass index [ (28±4) vs (34±4) kg/m²] were significantly improved in operation group (z=2.38-6.70, all P<0.05). After surgery, all five questions (Q1-Q5) for food addiction were significantly improved compared with preoperation (s=13.00-28.00, all P<0.05). Compared with control group, the three questions (Q1, Q2, Q3) were greatly improved in operation group (z=2.85-3.29, all P<0.05). The average difference between the operation group and the control group was Q1: 0.71 vs 0.34, Q2: 0.73 vs 0.32, Q3: 0.65 vs 0.29, respectively.

Compared with traditional medical treatment, bariatric surgery may significantly improve the food addiction of obese patients with T2DM in addition to lower blood sugar, body weight.

To analyze the relationship between serum 25-hydroxy vitamin D[25(OH)D] level and glycated hemoglobin A_1c(HbA_1c) level in a Urumqi Uygur and Han community.

A total of 2 080 cases from a diabetes epidemiological survey conducted in a Urumqi community from May to June 2013 were used. Altogether 1 665 Uygur and Han cases with complete data were included for this study (Uygur/Han: 719/946; male/female: 502/1 163) , with ages ranging from 18 to 82 years old, average age [Uygur/Han: (44±13) / (48±16) years old]. Serum 25 (OH) D level and HbA_1c concentration were measured. The correlation between 25(OH)D level and HbA_1c level was analyzed. The correlation between ethnics, gender and diabetic status was analyzed. The single factor analysis of variance, t test and Pearson correlation analysis were used for statistical analysis.

(1) The 25(OH)D level of Uygur was significantly lower than that of Han[(13+7) vs (19±8) μg/L, t=16.543, P<0.001]; male had significantly higher 25(OH)D level than female [(18±7) vs (16±9) μg/L, t=5.413, P<0.001]. Uygur had greatly higher HbA_1c level than Han [ (6.0±1.4) % vs (5.8±1.2)%, t=-2.356, P=0.012], no statistical difference was found between men and women (P>0.05). (2) In Uygur male subjects with adequate 25 (OH) D level, lack of 25(OH)D level or insufficient 25(OH)D level, the HbA_1c were different (F=11.763, P<0.001). (3) Correlation analysis found that in Uygur male, 25(OH)D was positively related to HbA_1c level (r=0.157, P=0.029) and the difference did not change after controlling for age (r=0.228, P=0.001) .

In Uygur male subjects, the 25(OH)D level is positively correlated with HbA_1c level although the correlation is small.

To determine the molecular characteristics and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolated from nasal swabs among patients with type 2 diabetes in community.

Nasal swabs were collected from 417 patients with type 2 diabetes in 11 communities of Lishui Town, Foshan City, from April 2014 to June 2014. Staphylococcus aureus was determined after bacteria isolation and identification. Cefoxitin disk diffusion test and mecA gene polymerase chain reaction (PCR) assay were applied to detect MRSA. The staphylococcal cassette chromosome mec (SCCmec) typing of MRSA was conducted by multiplex PCR assay and the sequence type (ST) typing of MRSA was determined by multilocus sequence typing (MLST) based on the sequence of 7 housekeeping genes of MRSA. The antibiotic susceptibility of MRSA was tested by K-B disk diffusion.

A total of 22 MRSA strains were isolated from the nasal swabs of 417 patients, including 1 strain of SCCmecⅠ (4.5%), 3 strains of SCCmecⅡ (13.6%), 3 strains of SCCmecⅢ (13.6%), 6 strains of SCCmec Ⅳ (27.3%), 4 strains of SCCmecV (18.2%) and 5 strains non-typeable (22.8%). Sixteen STs were found with MLST, of which 70% were ancestral ST for each clonal complex. MRSA isolates had high resistance rates to erythromycin, teicoplanin, clindamycin, moxifloxacin, tobramycin (81.8%, 59.1%, 59.1%, 36.4% and 31.8%, respectively), and all of MRSA isolates but 1 strain of SCCmec Ⅳ were sensitive to linezolid. And 68.2% of MRSA isolates were multi-drug resistant bacteria.

MRSA colonization is found in noses of patients with type 2 diabetes in community. The gene variation of MRSA isolates is low and its evolution is stable. Linezolid should be the prior choice for community infection of MRSA.

To explore the mechanism and effects of globular adiponectin (gAd) on atherosclerosis in rats with type 2 diabetes mellitus (T2DM).

Ninety male Sprague-Dawley rats were divided into control group (group N, n=24) and T2DM model group (n=66) according to the method of random number table. Similarly, 53 successful modeling diabetic rats were randomly divided into T2DM group (group D, n=26) and intervention group (group A, n=27). Rats in group A were administrated with gAd in dose of 10 μg·kg ^-1·d^-1, and rats in the other two groups were administrated with saline respectively. At the end of 4, 8 and 12 weeks (w), serum biochemical indexes were tested in 8 rats collected randomly from each group, respectively. In the mean time, atherosclerotic changes of thoracic aorta were observed by HE staining, and the expressions of type 1 collagen (Col-1) were detected by immunohistochemistry. The protein and mRNA expressions of transforming growth factor β1 (TGF-β1), Smad3, Smad7 were detected by Western blotting and real time fluorescent quantitative polymerase chain reaction, respectively. Statistical analysis was performed by using one way analysis of variance and LSD- t test.

In each period, compared with group N, in group D, atherosclerotic changes of thoracic aorta appeared, the lesions worsened gradually with staining time, and the expressions of TGF-β1, Smad3 and Col-1 increased significantly (12 w: 1.28±0.01 vs 0.99±0.02, 1.08±0.01 vs 0.84±0.01, 183.3±0.6 vs 200.7±2.1,t=25.108, 20.779, 15.011, all P<0.05), while the expression of Smad7 decreased (12 w: 0.72±0.02 vs 1.10±0.02, t=30.018, P<0.05). Compared with group D, in group A, atherosclerotic lesions of thoracic aorta were slight, and the expressions of TGF-β1, Smad3 and Col-1 decreased significantly (12 w: 1.05±0.01, 0.81±0.02, 196.3±1.2,t=19.913, 23.377, 11.258, all P<0.05), while the expression of Smad7 increased (12 w: 0.99±0.01, t=21.404, P<0.05). With the extending of gAd intervention, the atherosclerotic lesions mitigated, the expressions of TGF-β1, Smad3 and Col-1 decreased, Smad7 increased significantly (allP<0.05).

Globular adiponectin may inhibit the TGF-β1/Smads pathway by up-regulating Smad7 or down-regulating TGF-β1 and Smad3, and exert anti-fibrosis action in vascular wall to protect T2DM rats from atherosclerosis.

To investigate the effects of curcumin on peroxisome proliferators-activated receptor-alpha (PPAR-α)/carnitine palmitoyltransferase-1A (CPT-1A) signal pathway and lipid metabolism in hepatic tissue of acute hyperlipidemic rat, and elucidate the possible mechanisms.

The 5-6 week-old male SD rats were randomly divided into 6 groups: normal control group (NC, n=8), acute hyperlipidemia model group (Model, n=8), low-dose curcumin group (LC, 125 mg·kg^-1·d^-1, n=8), medium-dose curcumin group(MC, 250 mg·kg^-1·d^-1, n=8), high-dose curcumin group (HC, 500 mg·kg^-1·d^-1, n=8), and fenofibrate group (FF, 30 mg·kg^-1·d^-1, n=8). NC and Model groups were given gavage with corn oil(5 ml·kg^-1·d^-1) and the experimental groups (curcumin and fenofibrate) were given gavage with corresponding drug(dissolved by equal volume of corn oil) once daily for 10 days. Model, curcumin and FF group were injected intraperitoneally with 75% fresh egg yolk emulsion (25 ml/kg) to set up acute hyperlipidemia models (NC group rats were injected with equal volume of saline). After 24 h, blood samples were collected to detect the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and free fatty acids (FFA). The content of TG, FFA in hepatic tissue were detected by colorimetric method. Hematoxylin and eosin (HE) and oil red O staining were adopted to determine the morphological changes and fat mass of the hepatic tissue. The mRNA and protein expressions of PPAR-α, CPT-1A were detected with real-time polymerase chain reaction (PCR) and Western blotting methods. One-way analysis of variance was used when data were compared among multiple groups, and LSD test was applied when data were compared between two groups.

The blood levels of TG and FFA, hepatic contents of TG and FFA in LC/MC/HC groups decreased significantly than those in model group (t=2.196-27.350, all P<0.05); the swelling and vacuoles of the liver cell lessened and the proportion of lipid droplets reduced. The expression of PPAR-α and CPT-1A mRNA in Model group (0.009±0.003, 0.048±0.012) were both lower than those in NC group (0.022±0.003, 0.086±0.003) (t=-2.862, -30.262, both P<0.05), but the expressions were increased in curcumin groups than those in Model group (t=-22.870--5.509, all P<0.01). The protein expression of PPAR-α and CPT-1A in Model group (0.64±0.05, 0.128±0.012) were lower than those in NC group (0.98±0.09, 0.186±0.018) (t=-2.905--4.145, both P<0.05), but those were increased in curcumin groups (HC, MC, LC group) in a dose-dependent manner than those in Model group (t=-31.065--6.571, all P<0.01).

Curcumin can reduce serum lipid, improve liver lipid metabolism, thereby protect liver via up-regulating the PPAR-α/CPT-1A pathway.

To investigate Sestrin2/adenosine monophosphate-activated protein kinase (AMPK) induced autophagy in myocardial ischemia-reperfusion injury in diabetic rats and the protective effect of tert-butyl hydroquinone (TBHQ).

Healthy adult male SD rats were randomly divided into 6 groups (n=10): control rats with sham surgery group (NS), control rats with ischemia-reperfusion (NIR) group, control rats with ischemia-reperfusion+TBHQ group (NIPC), diabetes rats with sham surgery group (DS), diabetic rats with ischemia-reperfusion(DIR) group, diabetic rats with ischemia-reperfusion+TBHQ group(DIPC). Diabetes mellitus was induced by intraperitoneal injection of 60 mg/kg streptozotocin. TBHQ (40 mg/kg·d) was injected intraperitonealy to rats in TBHQ groups for 5 days before ischemia-reperfusion surgery. The myocardial ischemia-reperfusion model was induced by temporary ligation of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion. The change of myocardial tissue were observed by hematoxylin-eosin staining. The activities of serum creatine kinase isoenzyme (CK-MB) , lactate dehydrogenase (LDH) and superoxide dismutase (SOD) were determined by enzyme linked immunosorbent assay. The expression of Sestrin2, phosphorylated AMP activated protein kinase (p-AMPK) , Beclin1 and cysteine aspartic acid specific protease 3 (Caspase3) were detected by Western blotting. T-test or ANOVA analysis was used for data analyses.

Compared with group NIR, the activities of CK-MB and LDH were decreased(343±37 vs 453±36, 428±65 vs 576±45, t=0.006 6,0.013 4, all P<0.05), whereas the level of SOD was increased in group NIPC (706±17 vs 566±21, t<0.000 1, P<0.05). Sestrin2, p-AMPK, Beclin1 level were statistically higher and Caspase 3 was lower in NIPC group (t=0.000 4-0.005 6, P<0.05) compared with NIR group (t=0.000 9, P<0.05). Compared with group NS, the activities of CK-MB, LDH, SOD were highly expressed in group NIR and group NIPC (F=17.04-413.16, all P<0.05). Compared with group DS, the activities of CK-MB, LDH, SOD were highly expressed in group DIR and group DIPC (F=91.83-183.28, P<0.05), whereas Sestrin2, p-AMPK, Beclin1, Caspase3 were increased in groups NIR and NIPC (F=8.63-128.69, P<0.05). Compared with group DIR, the activities of CK-MB, LDH, Caspase3 were decreased in group DIPC (t=0.008 0-0.022 7, all P<0.05), but SOD, Sestrin2, p-AMPK, Beclin1 were increased in group DIPC (t=0.000 3-0.006 9, all P<0.05).

TBHQ alleviates myocardial ischemia-reperfusion injury by up-regulating Sestrin2/AMPK pathway which then activates authophagy in mitochondria.

To investigate the clinical features of idiopathic acquired generalized lipodystrophy (AGL) in one young female diabetic patient and to summarize the clinical experience in diagnosis and treatment of this disease.

The young female diabetic patient became thinner since childhood, however administration with overdosed insulin (4.3 U/kg body weight) could not get blood glucose well controlled [glycated hemoglobin A1c (HbA_1c) 10.7%]. Several explorations were performed to evaluate the severity of her insulin resistance and lipodystrophy.

This patient had obvious hyperinsulinemia (fasting insulin 54.7 mU/L, postprandial insulin 93.9 mU/L) and serious insulin resistance [glucose infusion rate 0.54 mg/(kg·min), normal range (11.56±1.74) mg/(kg·min)] after insulin administration suspended, as well as serious hypertriglycemia (14.08 mmol/L) and fatty liver. Serum adiponectin and leptin were 0.12 mg/L and 0.24 ng/L respectively, both were much lower than normal level. Various indicators of autoimmune disease were negative. Magnetic resonance imaging detected atrophy of adipose tissue in abdominal viscera and lower limbs. Skin biopsy showed serious lipodystrophy. With gradually increased insulin dosage (total daily dosage 170 U, 4.9 U/kg) combined with metformin and pioglitazone, her glycemic control improved (HbA_1c 7.1%-7.8%).

For young diabetic patient with very low body weight and serious insulin resistance, the differential diagnosis of lipodystrophy, one special type of diabetes mellitus, should be paid more attention.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by islet beta cell destruction, and is characterized by wasting and absolute insulin deficiency. Recent studies have shown that obesity and insulin resistance (IR) may also play an important role in T1DM. A U.S. multicenter registry study of 13,000 patients with autoimmune T1DM showed that approximately 20% and 10% of patients were overweight or obese^[1]。 Studies in Germany and Austria with more than 21,000 diabetic patients yielded similar results^[2]。 Moreover, IR may also increase the risk of cardiovascular disease (CVD) in patients with T1DM, and also play a certain role in the onset and/or acceleration of the deterioration of T1DM. This article mainly discusses the role of IR in the pathogenesis of T1DM.

Diabetic patients are often complicated with coronary heart disease at the same time. The incidence of heart-related complications and mortality increased significantly in these patients after surgery, which seriously affected the surgical outcome and prognosis^[1]。 Literature shows that about 50% of diabetic patients need surgical treatment for various reasons in their lifetime. Due to surgical trauma and stress, the incidence of perioperative complications is about 5 times higher than that of non-diabetic patients. The incidence of perioperative major cardiac adverse events in diabetic patients is as high as 6.9%, and the cardiac mortality rate is 0.9%^[2,3]。 Therefore, how to alleviate myocardial ischemia/reperfusion (I/R) injury during cardiac surgery in diabetic patients and carry out effective myocardial protection is an urgent problem.

diabetic retinopathy (DR) is a common diabetic complication that can cause blindness and develop slowly. It is composed of hyperglycemia, dyslipidemia, abnormal metabolic regulation, and inflammatory response^[1]And ischemia and other factors. At present, various techniques such as fundus photography, fluorescence angiography, B-ultrasound scanning ultrasound and optical coherence tomography have been used to detect, diagnose and evaluate such diseases. Clinically, the common methods for treating DR mainly include: photocoagulation, intraocular steroid administration, vitreoretinal surgery, and vitreous injection of vascular endothelial growth factor (VEGF) inhibitors. In the treatment, it was found that intravitreal injection of VEGF inhibitors has good efficacy in improving the vision of patients with diabetic macular edema (DME)^[2]。 Therefore, regulating the level of neurotrophic factors (NTF) in the retina is the most important treatment plan based on neuroprotection.

Diabetic foot disease is one of the difficult and severe complications of diabetes, which causes great physical and mental trauma to patients, and also brings heavy economic burden and ethical test to their families. Under the current medical conditions, the diagnosis and treatment of severe diabetic foot (Wagner grade 5 or patients with severe lower extremity angiosclerosis obliterans) is still very difficult. Therefore, at present, the focus of diagnosis and treatment of diabetic foot is still on prevention-mainly to prevent the occurrence of diabetic foot and to prevent the development of mild diabetic foot into severe diabetic foot. Our hospital is a top three hospital in Yunnan Province. Among the patients with diabetic foot admitted from 2010 to 2017, 82% of patients with severe diabetic foot came from community hospitals, prefecture-level or county-level hospitals. With the establishment of hierarchical diagnosis and treatment system, how to further improve the understanding and diagnosis and treatment level of diabetic foot in primary medical institutions is an important cornerstone to ensure the smooth development of diabetic foot prevention, diagnosis and treatment and referral. The following describes the problems and countermeasures in the diagnosis and treatment of diabetic foot in primary medical institutions.

The prevalence of diabetes in China has reached 9.7%^[1]The number of patients ranks first in the world^[2]。 Diabetes mellitus and its associated complications impose a huge economic burden on health and hygiene on society. Patients with type 2 diabetes mellitus (T2DM) have 2 to 4 times higher risk of cardiovascular disease (CVD) than non-diabetic patients^[3]。 Although hyperglycemia has been proven to be an independent risk factor for CVD, there is no definitive conclusion as to whether intensive hypoglycemic therapy can reduce cardiovascular complications. The effects of intensive hypoglycemic therapy on cardiovascular outcomes varied due to differences in patient baseline, hypoglycemic goals, and follow-up time.