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Objective: Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM., Methods: A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (<0.9 vs. ≥0.9) and baPWV (<1,700 cm/s vs. ≥1,700 cm/s)., Results: The outcomes were all-cause mortality and composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation and diabetic foot). Inter-group differences in the smoking rate, duration of diabetes, systolic and pulse blood pressure, anti-platelet drugs, estimated glomerular filtration rate, and urine albumin excretion were significant. During the follow-up period, 17 (3.7%) individuals died and composite events were recorded in 64 cases (14.1%). A low ABI plus high baPWV was found be associated with poor outcomes compared with a normal ABI plus low baPWV (p<0.001). Meanwhile, a low ABI plus high baPWV was associated with an increased risk of all-cause mortality [hazard ratio (HR) 17.01, 95% confidence interval (CI) 1.57-183.73, p=0.019] and composite events (HR 8.53, 95% CI 3.31-21.99, p<0.001)., Conclusion: In this study, the outcomes of patients with a low ABI plus high baPWV were the worst, while the subjects with a low ABI plus low baPWV or normal ABI exhibited similar outcomes. Therefore, the ABI plus baPWV exhibits a better association with the outcomes of T2DM.

Objective: To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy., Research Design and Methods: Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10-14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and beta-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control., Results: At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 +/- 0.70% vs. 7.50 +/- 1.50%; P = 0.002). During the follow-up visit, the A1C level was still better in the insulin group (6.78 +/- 1.21% vs. 7.84 +/- 1.74%; P = 0.009). All parameters regarding beta-cell function measured in the OGTT were improved significantly in both groups after 6 months of treatment. Compared with the OAD group, the homeostasis model assessment of beta-cell function index, insulin area under the curve, and insulinogenic index were better in the insulin group., Conclusions: A 6-month course of insulin therapy, compared with OAD treatment, could more effectively achieve adequate glycemic control and significant improvement of beta-cell function in new-onset type 2 diabetic patients with severe hyperglycemia.

Aim: Self-monitoring of blood glucose (SMBG) is important for patients treated with insulin to detect asymptomatic hypoglycaemia and to guide patients towards reaching blood glucose goal. This study compared two management programs for adjusting bedtime insulin dose: program 1 (performed by study subjects) vs. program 2 (performed by study subjects and reminded by investigators)., Methods: This is a prospective, open-level, 28-week randomized trial in poorly controlled type 2 diabetic subjects. One hundred subjects treated with oral antidiabetic drugs plus bedtime insulin with glycated haemoglobin A(1C) (A1C) >8.0% were screened and received a structure education package in a 4-week run-in period. Seventy-eight subjects were randomized to two treatment programs (adjust insulin dose by themselves with or without investigators' reminder) and reviewed by the investigators at a 4-week interval clinical visit., Results: The mean SMBG decreased significantly in both groups, with a greater decrease observed in program 2 vs. program 1 (from 198.7 +/- 43.1 to 122.6 +/- 21.9 mg/dl vs. from 194.0 +/- 42.7 to 151.6 +/- 37.7 mg/dl, p < 0.001). Bedtime insulin dose increased in both groups with a greater increase in program 2 (from 14.4 +/- 8.7 to 27.4 +/- 12.8 IU vs. from 14.3 +/- 8.3 to 18.4 +/- 6.2 IU, p < 0.001). There was a significant reduction in A1C from 9.54 +/- 1.67% to 7.76 +/- 1.27%, with a greater decrease (p < 0.001) in program 2 (2.17%) than in program 1 (1.40%). There were more subjects in the program 2 group achieving the treating targets: mean SMBG < or =120 mg/dl (46.9 vs. 17.9%) and A1C < or =7.0% (54.5 vs. 32.2%). There was no significant difference in the incidence of hypoglycaemia and body weight changes., Conclusions: Systematically titrating bedtime insulin dose added to oral therapy, especially combined with health care reminders, can safely improve glycaemic control in type 2 diabetes with poor glycaemic control. This regimen may facilitate safe and effective insulin therapy in routine medical practice and improve achievement of recommended standards of diabetes care.

Objective: To investigate whether the effects of regular diabetes health education or a holiday-specific pamphlet before the Chinese New Year holiday period could improve glycemic control during the winter holidays among patients with type 2 diabetes mellitus., Study Design: Randomized controlled trial., Methods: The study was conducted from October 2004 to December 2005 in Taipei Veterans General Hospital. Subjects were randomized to program 1 (receipt of regular diabetes education between October 20 and November 25, 2004, and then every 3-4 months) or to program 2 (receipt of a special reminder pamphlet during the holidays). The patients were seen and blood samples obtained on 4 occasions during the holidays and then every 4 months through December 2005., Results: Ninety-three subjects completed the first 4 visits during the Chinese New Year holidays, and 89 subjects completed 12 months of the study. Fructosamine levels in program 1 increased more during the preholiday period than those in program 2 (mean [standard deviation] 7.4 [5.2] vs -5.3 [8.3] mumol/L, P = .03) during the preholiday period. Changes in fructosamine levels during the holiday and postholiday periods were similar in the 2 groups. At the end of the holidays, changes in glycosylated hemoglobin (A1C) levels were 0.34% (95% confidence interval, 0.03%-0.85%) in program 1 and 0.09% (95% confidence interval, -0.23% to 0.42%) in program 2. After the Chinese New Year holidays, the groups had similar changes in A1C levels, with a slight downward decline thereafter., Conclusion: A special educational reminder pamphlet for the holidays led to improvements in glycemic control during the Chinese New Year holidays.

Aims: The purpose of this study was to determine the relationship between subclinical hypothyroidism and prevalence of retinopathy and nephropathy, incident cardiovascular disease, and mortality in Type 2 diabetic patients without taking thyroid medication., Methods: Serum thyrotropin and free thyroxine concentrations were measured in 588 Type 2 diabetic subjects in Taipei Veterans General Hospital, Taiwan. In a cross-sectional study, we examined the prevalence of retinopathy and nephropathy. In a longitudinal study, we examined the risk of cardiovascular disease events, cardiovascular mortality and total mortality in the 4-year follow-up., Results: In the cross-sectional analysis, subclinical hypothyroidism was associated with a greater prevalence of diabetic nephropathy (odds ratio, 3.15 [95% CI, 1.48-6.69]) and did not show a high prevalence of diabetic retinopathy (odds ratio, 1.15 [95% CI, 0.59-2.26]) compare to euthyroid diabetics. During the 44.0 +/- 7.4 months of follow-up, 51 participants had cardiovascular events. The risk of cardiovascular events was significantly increased in Type 2 diabetics with subclinical hypothyroidism after adjustment for age, sex, A1C, other standard cardiovascular risk factors and medication (hazard ratio, 2.93; 95% CI, 1.15-7.48; P = 0.024), but it became nonsignificant after additional adjustment for urinary albumin-to-creatinine ratio (hazard ratio, 2.06; 95% CI, 0.67-6.36; P = 0.211). The rates of cardiovascular-related and total mortality did not significantly differ by thyroid status., Conclusions: Type 2 diabetic patients with subclinical hypothyroidism are associated with an increased risk of nephropathy and cardiovascular events, but not with retinopathy. Our data suggest that the higher cardiovascular events in subclinical hypothyroidism with Type 2 diabetes may be mediated with nephropathy.

Background: This study compares the cardiovascular autonomic function in type 2 diabetes with and without microalbuminuria, in order to identify the possible links between early nephropathy and diabetic autonomic neuropathy (DAN)., Methods: Cardiovascular reflex tests were performed to determine the cardiovascular autonomic function. Thirty cases of type 2 diabetes with microalbuminuria were studied for evidence of DAN to compare with a normoalbuminuric group of 56 diabetic patients., Results: There was an increased prevalence of autonomic dysfunction in patients with microalbuminuria (63.3% in the microalbuminuria group vs. 40.0% in the normoalbuminuric controls, p = 0.001). These patients had lower heart rate variability during single breathing tests (6.9 +/- 4.3 vs. 9.6 +/- 3.6 beats/minute, p = 0.005), during 6 consecutive breathings (5.8 +/- 3.6 vs. 8.2 +/- 3.3 beats/minute, p = 0.005), after standing up (12.2 +/- 4.6 vs. 15.0 +/- 5.2 beats/ minute, p = 0.012), and during the Valsalva maneuver (11.3 +/- 3.5 vs. 13.2 +/- 3.6 beats/minute, p = 0.022). The heart rate variability with these stresses was revealed to be less favorable in subjects with microalbuminuria. However, blood pressure (BP) changes from the sitting to standing position were not significantly different for systolic BP (11.5 +/- 10.7 vs. 10.7 +/- 7.8 mmHg, p = 0.741) and diastolic BP (5.2 +/- 4.4 vs. 5.9 +/- 4.0 mmHg, p = 0.451) between the 2 groups., Conclusion: Type 2 diabetic patients with microalbuminuria have diminished heart rate variability in response to deep breathing, change of position and the Valsalva maneuver, but they preserve BP response to postural change. Therefore, microalbuminuria seems to be associated with early DAN, but not with advanced DAN.

Objective: In the U.K. Prospective Diabetes Study, A1C increased from 1.2 to 1.7% and fasting plasma glucose from 1.0 to 2.8 mmol/l over 10 years in type 2 diabetic patients. It is not known whether the blood glucose increase observed in long-term studies of type 2 diabetes results from small, steady increases throughout the year or from increases during discrete periods., Research Design and Methods: To estimate the variation of actual glycemic control and its relation to holiday times, we measured A1C and fructosamine in 110 patients with type 2 diabetes. These measurements were performed four times at intervals of 4-6 weeks; therefore, glycemic change was determined for three periods: preholiday period (from between November 13 and December 20 to between December 20 and January 20), holiday period (from between December 20 and January 20 to between January 28 and February 28), and postholiday period (from between January 28 and February 28 to between March 1 and April 10). A final measurement of A1C was obtained from 90 subjects in the following December or January., Results: The mean A1C increased, but not significantly, during the preholiday (increase 0.135 +/- 0.723%, P = 0.055) and holiday (increase 0.094 +/- 0.828%, P = 0.239) periods. The mean A1C decreased, but not significantly, during the postholiday period (decrease 0.022 +/- 0.588%, P = 0.695). Altogether, the A1C change during these three periods increased significantly (increase 0.207 +/- 0.943%, P = 0.024). The mean fructosamine increased significantly during the preholiday period (increase 0.151 +/- 0.460 mmol/l, P = 0.001), but there was no significant change during the holiday period (increase 0.057 +/- 0.593 mmol/l, P = 0.321). However, fructosamine decreased significantly during the postholiday period (decrease 0.178 +/- 0.448 mmol/l, P < 0.001). Altogether, the fructosamine changes during the study periods showed no significant difference (increase 0.030 +/- 0.566 mmol/l, P = 0.579). Between March or early April and the following December or January, there was no additional change in A1C (decrease 0.009 +/- 1.039%, P = 0.935) for the 90 participants who returned for follow-up treatment., Conclusions: The present study demonstrates an influence of winter holidays on the glycemic control of patients who have type 2 diabetes, and this poor glycemic control might not be reversed during the summer and autumn months. Therefore, the cumulative effects of the yearly A1C gain during the winter holidays are likely to contribute to the substantial increase in A1C that occurs every year among type 2 diabetic individuals.

Aims: The goal of this study was to determine the frequency of mutation in hepatic nuclear factor (HNF)-1alpha, a gene recently implicated as causing maturity-onset diabetes of the young (MODY) and to analyse the respective clinical presentations in an ethnically Chinese population., Methods: Fifteen unrelated subjects (nine females and six males) aged less than 35 years who had early-onset diabetes were analysed to test the possibility that mutation of the HNF-1alpha gene was responsible for this disorder. Genomic DNA extraction, polymerase chain reaction and DNA sequence analysis were performed accordingly., Results: One patient with MODY had a novel missense mutation in exon 3 of the HNF-1alpha gene (Y218C) in a region of the protein that corresponds to a predicted DNA binding domain., Conclusions: A Y218C mutation in HNF-1alpha gene was identified in one family in Taiwan.

Plasma plasminogen activator inhibitor-1 (PAI) antigen, fibrinogen, antithrombin III (ATIII), protein C, beta-thromboglobulin (BTG), platelet count, fibrinogen degradation product (FDP) D-dimer, factors VII and XII, as well as cholesterol, triglyceride (TG) and glucose were determined in 163 subjects. First we compared the difference of these parameters between 50 diabetics (Group D, mean age 64.9 years) and 50 age-matched healthy controls (Group C, mean age 63.1 years). Nineteen of the diabetics and 19 of the healthy controls were smokers. Plasma glucose, cholesterol, TG and protein C were significantly higher in Group D than in Group C (p = 0.0010, 0.0308, 0.0083 and 0.0068, respectively), whereas ATIII and factor XII were significantly lower in Group D (p = 0.0213 and 0.0061). Secondly, we divided 113 healthy controls (Group C, including Group C plus 63 subjects at various ages) into smokers (mean age 56.7 years) and non-smokers (mean age 40.0 years) and compared the difference between them. Fibrinogen and glucose were higher in the smokers than in the non-smokers (p = 0.0139 and 0.0402, respectively). Other parameters were not different. In conclusion, our study did not find any important hypercoagulation state in the diabetics. Smoking can only increase fibrinogen and glucose without the change of other hemostatic parameters.

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.

This study aims to compare the effectiveness and immunogenicity of semisynthetic human insulin (NOVO) and highly purified (monocomponent) porcine insulin over a 12 month period in 16 non-insulin-dependent diabetic subjects not previously exposed to insulin. Sixteen patients were randomly allocated for treatment with either human (n = 9) or monocomponent porcine (n = 7) insulin in a double-blind trial. Both groups were identical with respect to age, sex and measures of metabolic control. Significant insulin antibody was detected in seven of the nine patients (78%) 3 months after the commencement of human insulin therapy whereas it was detected in all patients (100%) in the group treated with monocomponent porcine insulin as early as 2 months after insulin therapy. Besides the delayed rise of insulin antibodies during the first 3 months of human insulin therapy, it tended to have a lower mean insulin antibody titer, though statistically insignificant, at the end of the study. No adverse reaction to either type of insulins was noted. It is concluded that both semisynthetic human and monocomponent porcine insulin were safe and effective. Although human insulin showed a slightly lower immunogenicity than monocomponent porcine insulin of the same formulation and purities, it was not non-immunogenic. Hence, there is no reason to treat all insulin-requiring diabetic subjects with human insulin except those who have developed insulin allergy or those at risk or with a history of allergy.

Plasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C group, but the means of PAI were not significantly different among the 3 groups. ELT was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases.

A 23 year-old obese Chinese gentleman was admitted to our hospital with the main problem of conscious disturbance for one day. The physical examination and laboratory data confirmed that this is a case of diabetic ketoacidosis complicated with rhabdomyolysis resulting in acute renal failure three days after admission, and regained his renal function after intensive hemodialysis and other conservative treatment.