Volume 04 · Issue 03 · 2012

Diabetes mellitus and thyroid disease are the most common endocrine disorders, and the association between them has been reported as early as 1979^[1,2]。 On the one hand, thyroid hormones can regulate carbohydrate metabolism and pancreatic islet function; Diabetes, on the other hand, also affects thyroid function to some extent. The relationship between diabetes mellitus and thyroid disease is the focus of research at present. The relationship between them is the result of a series of signal transduction pathways, among which type 1 diabetes mellitus and autoimmune thyroid disease are also related to genetic predisposition^[3]。 The relationship between thyroid function and diabetes is briefly discussed.

Type 1 diabetes (specifically type 1A diabetes, that is, autoimmune diabetes) and autoimmune thyroid disease are relatively common autoimmune endocrine diseases, both of which are caused by organ-specific T lymphocyte-mediated autoimmune attack against the body's endocrine tissue. Type 1 diabetes is characterized by the occurrence of isletitis and the appearance of islet β-cell autoantibodies; Autoimmune thyroid disease is a group of diseases characterized by infiltration of thyroid lymphocytes and production of thyroid autoantibodies, mainly including chronic lymphocytic thyroiditis and Graves disease. About one-third of patients with type 1 diabetes have autoimmune attacks that are not limited to islet beta cells and can progressively develop into autoimmune polyendocrine syndrome^[1]。 Some scholars also believe that type 1 diabetes combined with autoimmune thyroid disease is a variant of type 3 autoimmune polyendocrine syndrome^[2]。 Type 1 diabetes and autoimmune thyroid disease tend to occur in the same individual, and they have a tendency to aggregate in families, suggesting that they have a close relationship in genetic pathogenesis.

Hypoglycemia is a clinical condition that causes the capture of energy supply to the brain, leading to brain dysfunction, and can be corrected within a certain range by increased blood sugar. Diabetic hypoglycemia refers to the phenomenon of hypoglycemia in diabetic patients during drug treatment. For non-diabetic patients, the diagnostic criteria for hypoglycemia is blood sugar<2.8 mmol/L, while blood glucose ≤3.9 mmol/L in diabetic patients receiving drug treatment belongs to the category of hypoglycemia^[1]。 Symptomatic hypoglycemia often occurs in patients receiving insulin therapy or taking hypoglycemic drugs (sulfonylureas or glinides) that promote insulin secretion, and is rare in patients with insulin-secreting tumors or liver failure. Mild symptoms of hypoglycemia can also occur after a long period of fasting in normal people. The clinical symptoms caused by hypoglycemia roughly include two categories: adrenaline-like action and central nervous system insufficiency symptoms. The former manifests as strong hunger, palpitations, excessive sweating, dizziness, trembling, weakness, etc. This syndrome is called acute neuropathic hypoglycemia, which is only seen when blood sugar rapidly drops to a certain threshold. These symptoms are all attributed to enhanced sympathetic nerve activity and increased adrenaline release^[2]。 CNS manifestations include behavioral abnormalities, restlessness, decreased orientation, visual impairment, stiffness, epilepsy, and disturbance of consciousness, among which disturbance of consciousness is the most common symptom of hypoglycemia^[3]。 The clinical manifestations of hypoglycemia depend on the magnitude, speed, duration of blood sugar decline and whether the patient has underlying diseases or has experienced hypoglycemia or even severe hypoglycemia. The clinical manifestations of mild hypoglycemia may not be obvious. If blood sugar continues to drop, it can cause sympathetic nerve excitation symptoms such as palpitations, sweating, muscle fibrillation, etc., and may be accompanied by brain dysfunction such as inattention, irritability, dizziness, headache, etc. Severe hypoglycemia can lead to defects in focal signs, epilepsy, mental abnormalities and disturbances of consciousness, and even death^[4]。

To investigate the relationship between thyroid function and glucose level in adults with subclinical hypothyroidism and euthyroid.

A total of 2751 subjects completed a questionnaire survey and measurement for blood pressure, height, body weight, waist circumference, thyroid stimulating hormone (TSH), free triiodothyronine (FT₃), free thyroxine (FT₄), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2-h glucose, triglyceride (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). According to the level of thyroid hormone, the subjects were divided into subclinical hypothyroidism group (n=193) and euthyroid group (n=2146). Those in the euthyroid group were further divided into low TSH group (n=352, TSH ≥0.3 to <1.0 mU/L), moderate TSH group ( n=916, TSH ≥1.0 to ≤1.9 mU/L) and high TSH group (n=944, TSH 1.9< to ≤4.8 mU/L). According to serum level of glucose, all the subjects were divided into normal glucose tolerance (NGT) group, impaired glucose regulation (IGR) group, and diabetes mellitus (DM) group. The relationship between thyroid function indexes and glucose was analyzed. Student'st test or Analysis of Variance was used for data analysis.

The level of OGTT 2-h glucose in the subclinical hypothyroidism group was significantly higher than that in the euthyroid group ((8.3±4.4) vs (7.7±4.2) mmol/L, t=-2.163, P<0.05). The level of FT₄ in the DM group was significantly higher than that in the IGR group and NGT group ((16.8±2.1), (16.3±2.1), and (16.2±1.9) pmol/L, respectively; F=10.515, P<0.01). The prevalence of subclinical hypothyroidism in the DM group and IGR group was significantly higher than that in the NGT group in females, and the prevalence of subclinical hypothyroidism in females was significantly higher than that in males. After adjusting for body mass index (BMI), waistline, blood pressure and lipids, the level of FPG was positively correlated with FT₄ in the total population (β=2.748, P<0.01). For males, the level of FPG was positively correlated with FT₄ (β=2.346, P<0.01). The level of OGTT 2-h glucose in females was correlated with FT₄ (β=2.748, P<0.01). Within the normal range, the higher level of FT₄ showed higher risk of diabetes (total population: odds ratio (OR)=1.142, 95% confidence interval (CI) 1.064 to 1.225, P<0.01; female:OR=1.147, 95% CI 1.024 to 1.284, P<0.05; male:OR=1.142, 95% CI 1.035 to 1.261, P<0.01). There was no correlation between TSH or FT₃ and diabetes.

The prevalence of subclinical hypothyroidism may be increased in female patients with IGR or DM.FT₄ could be positively correlated to blood glucose, and higher level of FT₄ might result in higher risk of diabetes.

To investigate the relationship of autoimmune thyroid disease (AITD) with islet autoantibodies, namely glutamic acid decarboxyase antibody (GADA), protein tyrosine phosphatase-2 antibody (IA-2A) and zinc transporter 8 antibody (ZnT8A).

A total of 521 AITD patients (male 107, female 414, age (41±14) y), 153 non-autoimmune thyroid disease (nAITD) patients (male 24, female 129, age (50±14) y) and 102 healthy controls (male 52, female 50, age (23±4) y) were enrolled in this cross-sectional and case-control study. The levels of GADA, IA-2A and ZnT8A were detected by radio immunoprecipitation assay according to international standards. Chi-square test or t test was used for data analysis.

(1) The prevalence of GADA and ZnT8A in the AITD group was 7.29% (38/521) and 16.70%(87/521), respectively, which was higher than that of the healthy controls (both 0.98% (1/102); χ ² values were 5.794 and 17.374, respectively; both P<0.05) and the nAITD group (GADA 2.14%(3/140), ZnT8A 9.93% (15/151); χ² values were 5.032 and 4.161, respectively; both P<0.05). The difference between IA-2A positive rate in the AITD group (4.22% (22/521)) and the healthy controls (0, χ²=3.311, P>0.05) or nAITD (2.14% (3/140), χ²=1.312, P>0.05) was not statistically significant. (2) In the AITD group, patients with two or more islet autoantibodies positive had a higher incidence of diabetes mellitus than islet autoantibodies negative ones (21.43% (3/14) vs 5.13% (20/390), Fisher test,P<0.05). In AITD patients, the prevalence of diabetes between one islet autoantibody positive (any of the three) participants and islet autoantibodies negative ones was of no statistical significance (6.87% (9/131) vs 5.13% (20/390), χ²=0.566, P>0.05). (3) The prevalence of positivity for any of the three islet autoantibodies was higher in AITD patients with high titer (≥600 U/ml) thyroid peroxidase antibody (TPOAb) than those with lower TPOAb titer (35.83% (43/120) vs 22.93% (86/375), χ²=7.851, P<0.01), and so was for GADA (14.17% (17/120) vs 4.8% (18/375), χ²=12.138, P<0.01).

AITD patients with high titer TPOAb may be prone to be islet autoantibodies positive, which indicates the association of AITD and autoimmune diabetes mellitus in the immunological pathogenesis.

To analyze the clinical characters of abnormal glucose metabolism in hypothyroid patients and its potential risk factors.

Twenty-six primary hypothyroidism patients who were admitted to the Department of Endocrinology in the First Affiliated Hospital of China Medical University from February 2008 to July 2010 and underwent oral glucose tolerance test (OGTT) were enrolled in this retrospective study. According to their medical records and blood glucose levels, the patients were assigned to three groups: group A, hyperglycemia occurred later than hypothyroidism (n=14); group B, hyperglycemia was found earlier than hypothyroidism (n=6); and group C, glucose metabolism was normal (n=6). Clinical data such as age, hypothyroid duration and blood glucose level were compared between the groups. Kruskal-Wallis or Fisher test was used for data analysis.

None of the patients developed hypoglycemia. All the patients in group A showed impaired glucose tolerance (IGT), while only 42.9% (6/14) had impaired fasting glucose (IFG). About 83.3% (5/6) patients in group B had diabetes mellitus, while 16.7% (1/6) only had IGT. OGTT 2-h blood glucose level in group A was obviously higher than that in group C ((9.3±0.3) vs (6.4±0.2) mmol/L, t=-7.390, P<0.01). There was an increasing trend in age and body mass index (BMI) in group C, A and B. BMI and age were independent risk factors of elevated OGTT 2-h plasma glucose.

Hyperglycemia was not rare in patients with primary hypothyroidism, and elevated post-load plasma glucose was the predominant pattern, which might be correlated with BMI and age.

To identify risk factors of diabetic foot (DF) in patients with diabetes mellitus.

All medical records of 662 DF inpatients (DFP group) and 353 diabetic inpatients without DF (non-DFP group) treated from January 1996 to December 2009 in West China Hospital were retrieved. There were 371 males and 291 females in DFP group with a mean age of (66±11) y, and 205 males and 148 females in non-DFP group with a mean age of (66±9) y. Chi-square test, univariate logistic regression analysis and multivariate and non-conditional logistic regression analysis were used to identify the risk factors of DF.

The incidence of diabetic nephropathy(DN), diabetic retinopathy (DR), peripheral arterial disease(PAD), diabetic peripheral neuropathy(DPN), diabetic autonomic neuropathy(DAN)in DFP group were higher than those in non-DFP group(χ²=34.133, 11.694, 165.727, 85.852, 72.021, respectively, all P<0.05). Lung infection and osteoporosis occurred more often in DFP group than in non-DFP group (χ²=32.619, 23.932, both P<0.05). The univariate logistic regression analysis revealed that smoking(Wald=4.874), DN (Wald=33.516), DR (Wald=11.581), PAD (Wald=146.356), DPN (Wald=82.446) and DAN (Wald=67.686) were risk factors for DF(allP<0.05), HDL-C (Wald=25.532,P<0.05) was protective factor against DF. Multivariate and non-conditional logistic regression analysis showed that DN (Wald=58.837), DPN (Wald=21.484), DAN (Wald=11.963) and PAD (Wald=87.427) were risk factors for DF(allP<0.05), HDL-C (Wald=14.971,P<0.05) was protective factor against DF.

It suggests that DN, DPN, DAN and PAD are associated with an increased risk of DF, while HDL-C is the protective factor against DF.

To evaluate the insulin sensitivity in a patient with Prader-Willi syndrome.

A 18-year-old man presented with progressive weight gain for 15 years was diagnosed as Prader-Willi syndrome. Hyperinsulinemic-euglycemic clamp was performed to evaluate the insulin sensitivity in this patient.

On admission, the patient's body weight and height was 115 kg and 156 cm respectively, and his body mass index (BMI) was 47.3 kg/m². The glycated hemoglobin (HbA1c) level was 6.8%. The results of oral glucose tolerance tests (OGTT) met the diagnostic criteria for diabetes mellitus. A delay peak of late-phase insulin secretion was found during OGTT: insulin level at 0, 60 and 120 min was 43.7, 247.6 and 230.9 mU/L, respectively. Thyroid and adrenal cortex function were all normal. In euglycemic clamp, the basal plasma glucose was 4.5 mmol/L, glucose infusion rate (GIR) was 6.6 and 6.2 mg/(kg·min) during 20~120 min and in stable phase, respectively.

It showed that Prader-Willi syndrome is associated with insulin resistance.

To explore whether carriers of a high frequency variant p. T60M of the Na-Cl cotransporter (NCC) gene have a phenotype similar to patients treated with low-dose thiazide diuretics.

From January 2009 to December 2010, 38 carriers of variant p. T60M of NCC from Gitelman syndrome (GS) families confirmed by our previous study and healthy subjects were enrolled in this study. Another 38 matched healthy adults were recruited as controls. Blood pressure and biochemistry data were detected. Na-Cl cotransporter econding gene was analyzed by directional sequencing. Student'st test and χ ² test were used for data analysis.

GS-heterozygotes showed significantly lower blood pressure (systolic blood pressure: (110±14) vs (119±15) mm Hg (1 mm Hg=0.133 kPa), t=2.686, P<0.01; diastolic blood pressure: (70±7) vs (75±8) mm Hg,t=2.944, P<0.01) and higher fasting plasma glucose ((5.4±0.7) vs (5.0±0.7) mmol/L,t=2.432, P<0.01) than the controls. Fourteen GS-heterozygotes and 6 control subjects had impaired fasting glucose. Those of GS-heterozygotes had higher 24-h urinary sodium excretion than the controls ((170±36) vs (160±39) mmol/24 h,t=1.286, P>0.05).

GS-heterozygotes have lower blood pressure and slightly higher fasting plasma glucose when compared with normal controls.

To examine the expression of G-protein coupled receptor 120 (GPR120) mRNA in abdominal subcutaneous and omental adipose tissues and related factors in obese subjects.

From September 2010 to August 2011, 39 non overweight subjects (body mass index(BMI)<23 kg/m²) and 40 obese patients (BMI>25 kg/m² ) who underwent cholecystectomy in the Third Affiliated Hospital of Guangzhou Medical College were enrolled in this study. Body weight, waist-hip ratio (WHR), blood glucose, and lipids, etc, were measured. The expression of GPR120 mRNA in abdominal subcutaneous and omental adipose tissues were measured by RT-PCR. The t test, Pearson correlation analysis, partial correlation analysis and multi-stepwise regression were used for data analysis.

(1) In obese and control group, the GPR120 mRNA expression in omental adipose tissue (0.876±0.076, 0.621±0.052) were significantly higher than those in subcutaneous adipose tissue (0.479±0.028, 0.421±0.035, t =-2.546 or -2.211, respectively, both P<0.05). The GPR120 mRNA expression in omental adipose tissue(0.876±0.076) was significantly higher in obese group than that in control group (0.621±0.052,t=-2.348, P<0.05). The differences in the expression of GPR120 mRNA in abdominal subcutaneous adipose tissue between the two groups were not significant(0.479±0.028 vs 0.421±0.035,t=-0.584, P>0.05). (2) Multi-stepwise regression analysis demonstrated that the expression of GPR120 mRNA in omental adipose tissue was significantly correlated with HOMA-IR and WHR (R²=0.3730, standard partial regression coefficient were 0.227 and 0.321, respectively). The expression of GPR120 mRNA in abdominal subcutaneous adipose tissue was not correlated with other factors.

The GPR120 mRNA expression in abdominal omental adipose tissue was significantly higher in obese subjects than that in control group. Abdominal obesity and HOMA-IR were the main independent factors influencing the expression of GPR120 mRNA in omental adipose tissue.

To explore the influence of the rising blood glucose level on brain injury in rats after insulin-induced hypoglycemia.

A total of 30 Wistar rats(weight: (300±50) g, age: 4 months) were simpling randomly divided into three equal groups: experimental group(20 rats), both vehicle control group (group A, 5 rats)and normal control group (group B, 5 rats). According to the blood glucose concentration after reperfusion, 20 rats from the experimental group were sub-divided into four groups: 1<blood sugar≤3 mmol/L(group C, 5 rats), 3 mmol/L<blood sugar≤6 mmol/L(group D, 5 rats), 6 mmol/L<blood sugar≤9 mmol/L(group E, 5 rats), blood sugar>9 mmol/L(group F, 5 rats)(blood sugar=blood glucose level). TUNEL staining was used to detect the neurons undergoing apoptosis, and Fluoro-Jade (FJB)staining was performed to reveal the degenerating neuronal cell bodies and axons. SAS 8.0 software analysis and processing, staining between the two groups of measurement data using single factor analysis of variance data.

(1) TUNEL staining: the percentage of apoptotic neurons showed an obvious increase from C, D, E, and F group(hippocampal CA1: 40.2±3.1, 38.7±2.4, 36.8±2.6 and 76.4±6.3; hippocampal DG: 62.4±4.2, 59.8±3.7, 68.1±2.8 and 125.4±5.8)compared to group A and group B(hippocampal CA1: 3.2±1.9, 2.8±0.8; hippocampal DG: 4.1±2.4, 3.4±1.2), the difference was statistically significant(hippocampal CA1: F=13.52, P<0.05; hippocampal DG:F=14.29, P<0.05); among the subgroups from the experimental group, the percentage of apoptotic neurons from group F(hippocampal CA1: 76.4±6.3, hippocampal DG: 125.4±5.8)rose more markedly than the other three groups(group C, D, E, hippocampal CA1: 40.2±3.1, 38.7±2.4, 36.8±2.6; hippocampal DG: 62.4±4.2, 59.8±3.7, 68.1±2.8), the difference was statistically significant(hippocampal CA1:F=5.08, P<0.05; hippocampal DG:F=6.52, P<0.05). (2) FJB staining: there was a statistical significance between group A, B and group C, D, E, F (hippocampal CA1:F=18.49, P<0.05; hippocampal DG:F=11.37, P<0.05); furthermore, compared with group C, D, E, the percentage of FJB positive cells in group F was significantly increased., the difference was statistically significant(hippocampal CA1:F=7.83, P<0.05; hippocampal DG:F=14.29, P<0.05).

Control the rats on the same level of blood glucose and the same duration of the hypoglycemia, the severity of brain injury is closely correlated to the rising blood glucose concentration after hypoglycemia: the higher glucose level is, the more serious imparement brain suffer.

Type 1 diabetes is mainly divided into 2 types: type Ia, which is related to autoimmunity; Type IB, the etiology of which is currently unknown. This article will mainly discuss type IA type 1 diabetes. Type 1 diabetes is an organ-specific autoimmune disease, and patients are prone to other autoimmune diseases, the most common of which is autoimmune thyroid disease. 20% of patients with type 1 diabetes are positive for thyroid peroxidase antibodies or thyroglobulin antibodies, and nearly half of them will develop clinical autoimmune thyroid disease^[1]。 In contrast, 2.3% of children with autoimmune thyroid disease were positive for islet cell antibodies, compared with 0 in normal children^[2]。 In fact, when type 1 diabetes and autoimmune thyroid disease occur in the same individual, we call it autoimmune polyendocrine syndrome type III.

The concept of proteome was first developed by Australian scholars Wilkins et al^[1]First proposed in 1994, derived from the integration of protein and genome, refers to all proteins present in a cell. Proteomics, as an important core of functional genomics and the central field of life science research in the "post-genome era", has the task of deepening the understanding of the functions of all genes contained in the genome, paying attention to the expression changes of all proteins in a cell of an intact biological individual at a specific time or under specific environmental conditions, in order to find specific targets or genes that can interfere with such changes. Studies have shown that plasma contains a large number of rich and variable proteins, and has a series of important physiological functions. It is the "largest" and "deepest" proteome of human beings^[2]At present, research also shows that during the occurrence and development of diseases, plasma will produce differentially expressed proteins, and changes in the concentration of specific proteins in plasma often play an important early warning role in the occurrence and development of diseases^[3]。 Therefore, the quantitative and dynamic detection of organisms by plasma proteomics is of great significance for revealing the pathogenesis of diseases, discovering molecular markers, early diagnosis and individualized treatment. At present, with the continuous development of proteomics research technology and the continuous improvement of bioinformatics, proteomics has been widely used in the study of serum of major diseases such as tumors and cardiovascular diseases. However, it is still in the initial stage in the study of type 2 diabetes mellitus (T2DM) and its complications. This paper reviews the application of plasma proteomics in the study of T2DM.

High conductivity calcium activates potassium ion channels, namely BK_CaChannel, first discovered in bovine chromaffin cells in 1981, its alpha subunit was cloned and expressed from Drosophila in 1991. Because the mutation at the alpha subunit site is associated with calcium-activated potassium currents in muscles and neurons, it is also called dSlo channel^[1]And subsequently cloned on mammals, humans, and nematodes. Follow-up studies demonstrated that BK_CaChannels are widely distributed in various tissue cells, most in dog and human smooth muscle cells^[2]。 In recent years, the application of patch clamp technology has been used for BK_CaTechnical support was provided for the study of electrophysiological properties of channels, BK_CaFunctional changes of channels in various disease states have become new research hotspots.

The "3rd International Forum on Blood Glucose Monitoring" was held in Hangzhou on December 11th, 2011. The meeting was sponsored by Diabetes Branch of Chinese Medical Association and hosted by Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine.

Gastric bypass (GBP) is associated with postprandial hyperinsulinemia, and this effect is more pronounced in patients with recurrent hypoglycemia after surgery. Plasma glucagon-like peptide-1 (GLP-1) levels were significantly increased after GBP, suggesting that this response was involved in altered postprandial blood glucose regulation. The purpose of this study was to clarify the role of GLP-1 on insulin secretion in patients with GBP.

Glucagon-like peptide-1 (GLP-1) is an incretin that induces glucose-dependent insulin release and also has neurotrophic effects. The purpose of this study was to clarify the expression and activity of GLP-1 receptor in peripheral nerves, and to evaluate the role of GLP-1 receptor agonists in diabetic neuropathy.

Glucagon-like peptide-1 (GLP-1) is a concern in the treatment of type 2 diabetes, and the antidiabetic drug metformin increases circulating GLP-1 levels, but the mechanism is unclear. The aim of this study was to evaluate the direct effect of metformin or aminoimidazole carboxamide nucleotides on GLP – 1 secretion in murine – human NCI – H716 cells and rat L cells.

Forkhead-like transcription factor 1 (FoxO1) is an important transcriptional effector in the glucagon-like peptide-1 (GLP-1) signaling pathway, and FoxO1 activity depends on deacetylation regulated by silencing regulator 1 (SirT1). The purpose of this study was to observe the possible function of SirT1 in the action of GLP – 1.

Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analogue for the treatment of type 2 diabetes. GLP-1, including liraglutide, can pass through the blood-brain barrier and improve brain function. The purpose of this study was to demonstrate that the application of liraglutide in obese and insulin resistant mice induced by high fat diet in addition to hypoglycemic effect, can also improve cognitive function of mice.

Glucagon-like peptide-1 (GLP-1) can promote the proliferation and regeneration of pancreatic islet β cells, and has a strong effect on promoting insulin secretion. We hypothesized that increasing the expression of GLP-1 before the onset of diabetes will increase the number of islet cells, delay the onset of diabetes, and prolong the survival of BB rats.