Demographic and clinical characteristics of patients with type 1 diabetes mellitus: A multicenter registry study in Guangdong, China.

BACKGROUND: A lack of demographic and clinical data hinders efforts of health care providers in China to support patients with type 1 diabetes mellitus (T1D). Therefore, the aim of the present retrospective study was to provide an overview of the demographic and clinical characteristics of Chinese patients with T1D. METHODS: Hospital medical records of patients with T1D (diagnosed between January 2000 and December 2011) in 105 secondary and tertiary hospitals across Guangdong province were reviewed. Data were collected on patient age at diagnosis, presentations at onset, physical examination, and diabetes management. RESULTS: In all, 3173 patients diagnosed with T1D between January 2000 and December 2011 were included in the study (46.2% female). The median age at diagnosis was 27.5 years (interquartile range [IQR] 18.0-38.0) years and the median body mass index (BMI) at onset was 19.6 kg/m2 (IQR 17.4-21.8 kg/m2 ). Among adult patients, 0.9% were obese, 6.6% were overweight, 62.3% were normal weight, and 30.3 % were underweight. The prevalence of diabetic ketoacidosis (DKA) at onset was 50.1%. The proportion of patients with retinopathy, nephropathy, and neuropathy was 8.1%, 20.7 %, and 11.1%, respectively. CONCLUSION: The adult-onset form of T1D is not rare in China. The registry participants were characterized by older age at onset, lower BMI, and a higher prevalence of DKA at onset compared with those in regions with a high incidence of T1D, such as northern Europe. These findings contribute to a better understanding of the heterogeneity of T1D in different populations and so will help healthcare providers to develop management models that are more suitable for these patients.

Glucagon-like peptide 1 potentiates glucotoxicity-diminished insulin secretion via stimulation of cAMP-PKA signaling in INS-1E cells and mouse islets.

Glucagon-like peptide-1 (GLP-1)-enhanced insulin secretion is mainly mediated by cAMP-PKA and cAMP-Epac2 signaling pathways at physiological glucose concentrations. However the cellular mechanisms underlying the insulinotropic action of GLP-1 at glucotoxicity remain largely unknown. In the present study, we examined the effects of GLP-1 on glucotoxicity-diminished insulin secretion and explored the roles of these two cAMP-linked pathways in mediating the effects of GLP-1 under glucotoxic conditions. Consistent with the previous reports, exposure of INS-1E cells and mouse islets to 30 mM glucose for 72 h almost abolished glucose-stimulated insulin secretion. Addition of 10nM GLP-1 significantly increased glucose-stimulated insulin secretion. This was not due to a protective effect of GLP-1 against glucotoxicity-induced apoptosis but instead improvement of the secretory capacity of the insulin-secreting ß-cells. It is of note that GLP-1 preferentially increased the expression and activity of PKA, whereas had no effects on Epac2 at high glucose. In correlation with the observations, treatment of INS-1E cells with the specific PKA inhibitor Rp-cAMPS completely abolished the insulinotropic action of GLP-1, whereas knock-down of Epac2 did not interfere the effects of GLP-1. Moreover, GLP-1 did not increase further insulin secretion in the presence of the PKA agonist 6-Bnz-cAMP-AM. By contrast, it produced additional enhancement of insulin secretion when Epac2 was maximally stimulated by its selective agonist 8-pCPT-2'-O-Me-cAMP-AM. Taken together, our results suggest that GLP-1 potentiates glucotoxicity-diminished insulin secretion mainly through cAMP-PKA signaling pathway.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.

[The effects of glycemic control on ophthalmic refraction in diabetic patients].

OBJECTIVE: To evaluate effects of glycemic control on refraction in diabetic patients. METHODS: Twenty newly diagnosed diabetic patients were included in this study. The random blood glucose, glycosylated hemoglobin A1c (HbA1c) levels, fasting C-peptide and postprandial 2 h C-peptide levels were measured before treatment. The patients with random blood glucose ≥ 12.0 mmol/L and HbA1c ≥ 10.0% were selected. Refraction, intraocular pressure, radius of the anterior corneal curvature, depth of the anterior chamber, lens thickness, vitreous length, and axial length were measured on admission and at the end of week 1, 2, 3 and 4 during glycaemic control. RESULTS: A transient hyperopic change occurred in all the patients receiving glycemic control with a mean maximum hyperopic changes of 1.6 D (0.50 D ∼ 3.20 D). There was a positive correlation between the magnitude of the maximum hyperopic changes and the HbA1c levels on admission (r = 0.84, P < 0.05). There was a positive correlation between the magnitude of the maximum hyperopic changes and the daily rate of blood glucose reduction over the first 7 days of the treatment (r = 0.53, P < 0.05). There was no significant correlation between the magnitude of the maximum hyperopic changes and the levels of random blood glucose on admission. No significant correlation was observed between the maximum hyperopic changes and fasting C-peptide or postprandial 2 h C-peptide. There were no significant correlations between the magnitude of the maximum hyperopic changes and age, blood press, body mass index, triglyceride, total cholesterol, low-density lipoprotein or high-density lipoprotein. No significant changes were observed in the intraocular pressure, radius of the anterior corneal curvature, depth of the anterior chamber, lens thickness, vitreous length and axial length during glycemic control. CONCLUSIONS: Transient hyperopic changes occur after glycemic control in diabetic patients with severe hyperglycaemia. The degrees of transient hyperopia are highly dependent on HbA1c levels before treatment and the rate of reduction of glucose level over the first 7 days of treatment. This is probably due to the decrease of refractive power by lens hydration, not morphological change of lens.

Effects of glycemic control on refraction in diabetic patients.

AIM: To evaluate the effects of glycemic control on refraction in diabetic patients. METHODS: Twenty newly diagnosed diabetic patients were included in this study. The random blood glucose, HbA1c levels, fasting C-peptide and postprandial 2h C-peptide were measured before treatment. The patients with random blood glucose higher than 12.0mmol/L and HbA1c level higher than 10.0% were selected. Refraction, intraocular pressure, radius of the anterior corneal curvature, depth of the anterior chamber, lens thickness, vitreous length, and axial length were measured on admission and at the end of week 1, 2, 3 and 4 during glycemic control. RESULTS: A transient hyperopic change occurred in all the patients receiving glycemic control. The maximum hyperopic change was 1.60D (range 0.50±3.20D). Recovery of the previous refraction occurred between two and four weeks after insulin treatment. There was a positive correlation between the maximum hyperopic changes and the HbA1c levels on admission (r=0.84, P<0.05). There was a positive correlation between the maximum hyperopic changes and the daily rate of blood glucose reduction over the first 7 days of the treatment (r=0.53, P<0.05). During transient hyperopia, no significant changes were observed in the intraocular pressure, radius of the anterior corneal curvature, depth of the anterior chamber, lens thickness, vitreous length and axial length. CONCLUSION: Transient hyperopic changes occur after glycemic control in diabetic patients with severe hyperglycemia. The degrees of transient hyperopia are highly dependent on HbA1c levels before treatment and the rate of reduction of the blood glucose level.

[Evaluation of insulin resistance in type 1 diabetes with euglycemic-hyperinsulinemic clamp].

OBJECTIVE: To investigate insulin resistance in type 1 diabetes (T1DM) with euglycemic-hyperinsulinemic clamp. METHODS: Eight cases of newly diagnosed T1DM and 8 cases of newly diagnosed type 2 diabetes (T2DM) were selected. Their insulin sensitivity index (ISI) was evaluated with euglycemic-hyperinsulinemic clamp after 2 week insulin intensive treatment and compared with that of 10 healthy volunteers (normal control group, NC group). RESULTS: Age, BMI, fasting insulin (FIns), fasting C-peptide in the T1DM group were significantly lower than those in the NC group, while waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, HDL-C were not significantly different between the T1DM and NC groups. Age, BMI, WHR, FIns, fasting C-peptide, SBP, TC, TG in the T1DM group were significantly lower than those in the T2DM group. The ISI of the NC, T1DM and T2DM groups were 12. 83 +/- 1.09, 9.95 +/-0.50, 3.80 +/- 0.20, respectively. There was significant difference among the three groups (P < 0.05). CONCLUSION: The ISI in T1DM was significantly lower than that in NC group, but higher than that in T2DM.

[Evaluation of insulin secretion and insulin resistance by hyperglycemic clamp in Graves disease patients with impaired glucose tolerance].

OBJECTIVE: To investigate the state of insulin secretion and insulin resistance in patients of Graves disease (GD) with impaired glucose tolerance (IGT) by hyperglycemic clamp. METHODS: Six cases of Graves disease with IGT were selected as GD + IGT group and ten healthy volunteers as normal control group (NC group). All the subjects were required to fast for 12 hours and then underwent hyperglycemic clamp to assay insulin secretion and insulin sensitivity. Glutamic acid decarboxylase antibody (GAD-A) was tested in all the subjects. RESULTS: Insulin secretion in GD + IGT group was significantly higher than that in NC group. The 1st phase insulin secretion (1PH) was (636.31 +/- 105.54) mIU/L vs (233.56 +/- 21.33) mIU/L, P = 0.001. The 2nd phase insulin secretion (2PH) was (146.68 +/- 25.00) mIU/L vs (67.06 +/- 6.23) mIU/L, P = 0.03. The maximal insulin secretion during 120 - 150 minutes (Ins(120 - 150)) was (195.05 +/- 32.94) mIU/L vs (87.64 +/- 9.78) mIU/L, P = 0.04. The hyperglycemic clamp insulin sensitivity index (average glucose metabolic rate during 120 - 150 minutes/Ins(120 - 150)) was significantly lower in GD + IGT group than that in NC group (11.52 +/- 1.90 vs 21.72 +/- 3.25, P = 0.04). GAD-A was negative in all subjects. CONCLUSION: Cases of GD with IGT show significant insulin resistance with compensated elevated insulin secretion.

[Evaluation of first phase insulin secretion by a nateglinide-intravenous glucose insulin release test in newly diagnosed type 2 diabetics].

OBJECTIVE: To evaluate the function of the first phase of insulin secretion of pancreatic B cells in newly diagnosed type 2 diabetics using nateglinide-intravenous glucose insulin release test (NG-IVGIRT). METHODS: NG-IVGIRT and intravenous glucose insulin release test (IVGIRT) were done in 8 patients with newly diagnosed type 2 diabetes mellitus and NG-IVGIRT was done in 8 normal people. Insulin and glucose of blood were determined at - 15, 0, 2, 4, 6, 8 and 10 min in NG-IVGIRT or IVGIRT. RESULTS: The response of 0 - 10 min insulin to NG-IVGIRT was significantly higher than that to IVGIRT in the diabetics. The response of insulin to NG-IVGIRT in the normal controls was much higher than that in the diabetics. The area under curve (AUC) of insulin to NG-IVGIRT was apparently elevated and the AUC of glucose to NG-IVGIRT reduced in the normal controls as compared with those in the diabetics. CONCLUSION: The results indicated that the reserve of first phase insulin secretion in newly diagnosed type 2 diabetics could be provoked in some degree by NG-IVGIRT and there was a big difference in the reserve of the first phase of insulin secretion provoked by NG-IVGIRT between newly diagnosed type 2 diabetics and normal people.

[The expression of G proteins alpha-subunit mRNA in different thyroid diseases].

OBJECTIVE: To investigate the expression of G proteins alpha subunit mRNA in different thyroid diseases. METHODS: Twenty-three thyroid specimens were obtained during surgery, 5 from patients with Graves' disease (GD), 7 from patients with multinodular goiter (MNG), 6 from patients with eufunctioning thyroid adenoma (EFTA) and 5 from patients with thyroid papillary cancer (TPC). The expression of stimulating and inhibiting G proteins alpha subunit mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The expression of G(s)alpha mRNA in TPCs (1.67 +/- 0.25) was significantly higher than that in normal thyroids (1.10 +/- 0.14) and MNGs (0.96 +/- 0.31), P < 0.05 and P < 0.01. The expression in GDs (1.47 +/- 0.11) and EFTAs (1.36 +/- 0.28) was significantly higher than that in MNGs (P < 0.05), but comparable to that in normal thyroids. (2) The expression of G(i)alpha-2 mRNA in GDs (0.68 +/- 0.26) was lower than that in MNGs (1.15 +/- 0.35), P < 0.05, but there was no difference in the expression of G(i)alpha-1 and G(i)alpha-3 mRNA among different thyroid diseases. CONCLUSION: The results indicated that G(s)alpha could play an important role in the pathogenesis of thyroid papillary cancer and G proteins had different expression in different thyroid diseases.