Root surface and coronal caries in adults with type 2 diabetes mellitus.

OBJECTIVES: To determine the effect of type 2 diabetes mellitus (DM) on coronal and root surface caries and to investigate some factors suspected of being related to or interacting with DM, that may be associated with coronal and root surface caries. METHODS: A stratified cross-sectional study was conducted in 105 type 2 diabetic patients and 103 non-diabetic subjects of the same age and gender. Coronal and root surface caries, exposed root surfaces, periodontal status, stimulated salivary functions, oral hygiene status, oral health behaviors, and counts of mutans streptococci and lactobacilli were measured. RESULTS: Type 2 diabetic patients compared with non-diabetic subjects had a higher prevalence of root surface caries (40.0% versus 18.5%; P = 0.001), a higher number of decayed/filled root surfaces (1.2 +/- 0.2 versus 0.5 +/- 0.1; P < 0.01) and a higher percentage of generalized periodontitis (98.1% versus 87.4%; P < 0.01); but the prevalence and decayed/filled surface of coronal caries was not significantly different (83.8% versus 72.8% and 8.0 +/- 9.4 versus 6.3 +/- 7.5 respectively). The factors associated with root surface caries included type 2 DM, a low saliva buffer capacity, more missing teeth, and existing coronal caries; whereas wearing removable dentures, more missing teeth, a high number of lactobacilli, and a low saliva buffer capacity were associated with coronal caries. CONCLUSION: Type 2 DM is a significant risk factor for root surface, but not for coronal caries. Periodontal disease should be treated early in type 2 diabetic subjects to reduce the risk of subsequent root surface caries.

Physiological and pathophysiological regulation of regional adipose tissue in the development of insulin resistance and type 2 diabetes.

AIM: To survey the latest state of knowledge concerning the regulation of regional adipocytes and their role in the development of insulin resistance and type 2 diabetes. METHODS: Data from the English-language literature on regional adipocytes, including abdominal, intramyocellular, intrahepatic and intra-islet fat as well as the adipokines and their relations to insulin resistance and type 2 diabetes, were reviewed. RESULTS: It is not the total amount of fat but the fat that resides within skeletal muscle cell (intramyocellular fat), hepatocytes and intra-abdominally (visceral fat), via systemic and local secretion of several adipokines, that influences insulin resistance. Among the adipokines that relate to insulin resistance, adiponectin and leptin appear to have clinical relevance to human insulin resistance and others may also contribute, but their role is still inconclusive. The intra-islet fat also adversely affects beta-cell function and number (beta-cell apoptosis), eventually leading to deterioration of glucose tolerance. The abnormal location of fat observed in patients with type 2 diabetes and their relatives is conceivably partly the results of the genetically determined, impaired mitochondrial fatty acid oxidative capacity. Restriction or elimination of the fat load by weight control, regular exercise and thiazolidinediones has been shown to improve insulin resistance and beta-cell function and to delay the development of type 2 diabetes. CONCLUSION: These data support the plausibility of an essential role of regional adipose tissue in the development of insulin resistance and type 2 diabetes.

The role of diminished beta cell reserve and insulin resistance in secondary sulfonylurea failure of type 2 diabetes mellitus.

INTRODUCTION: The correction of hyperglycemia by insulin treatment has been shown to ameliorate beta cell function and insulin sensitivity in SU failure patients, and there also appears to have disparity between tests of beta cell function among these patients. The objectives of this study were to determine beta cell secretory reserve and insulin resistance of secondary SU failure type 2 diabetic patients who had fairly good glycemic control compared with those who were SU responsive and the disparity of beta cell responses to glucose and non-glucose stimuli were examined in these two groups. SUBJECTS AND METHOD: Eight secondary SU failure, insulin-treated and 11 SU responsive type 2 diabetic patients who were matched for age, degree of obesity, duration of diabetes as well as HbAlc were studied. Intravenous glucagon and oral glucose tolerance tests (OGTT) as well as short intravenous insulin tolerance test using arterialized venous blood were randomly performed on separate occasions to assess beta cell secretory reserve and insulin sensitivity, respectively. RESULTS: Basal (0.37+/-0.05 (SEM) vs 0.80+/-0.14 nmol/l; p=0.02) and stimulated c-peptide levels (0.66+0.08 vs 1.16+/-0.14 nmol/l; p=0.007) after glucagon as well as basal (0.46+/-0.06 vs 0.73+/-0.10 nmol/l; p=0.046) and maximal c-peptide responses (1.41+/-0.14 vs 1.97+/-0.14 nmol/l; p=0.021) to glucose stimulation were significantly lower in SU failure than SU responsive patients. However, the incremental changes of c-peptide over basal after glucagon (0.29+/-0.06 vs 0.37+/-0.09 nmol/l) and glucose (AUC: 36.9+/-7.6 vs 47.9+/-4.5 nmol/l/h) were not different between both groups. There were strong positive relationships between basal and stimulated c-peptide responses to glucagon (r=0.818; p=0.002) and glucose (r=0.85; p=0.001) in SU responsive patients but these relationships were not as strong in SU failure patients (r=0.682; p=0.062 and r=0.41; p=NS, respectively). Insulin sensitivity did not differ between the two groups. CONCLUSION: This study demonstrated that decreased basal, but not stimulated, insulin secretion was possibly a major factor associated with secondary SU failure in type 2 diabetic patients. With comparable glycemic control, there was no disparate beta cell responses to glucose and glucagon in patients with or without secondary SU failure.

Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies.

OBJECTIVE: To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD(65)Ab). METHODS: Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD(65)Ab were compared between patients with and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control group. RESULTS: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease. CONCLUSIONS: About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD(65)Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.

The utility of conventional dipsticks for urinary protein for screening of microalbuminuria in diabetic patients.

The demonstration that microalbuminuria is predictive of overt diabetic nephropathy has created a demand for the routine measurement of urinary albumin in diabetic patients. We assessed the sensitivity, specificity, positive and negative predictive values of the conventional dipsticks for urinary protein (Ames Multistix, Bayer Diagnostic, Australia) as the screening test for microalbuminuria in diabetic patients compared with Micral-Test II (Boehringer Mannheim, Germany). Radioimmunoassay for albumin was taken as standard for comparison. With the urinary albumin concentration of 20 mg/L as a discriminating level of microalbuminuria, Micral-Test II had a sensitivity of 98.8 per cent and a specificity of 68.6 per cent whereas Ames Multistix had lower sensitivity but higher specificity. If urinary albumin concentration of 60 mg/L was used instead as a discriminating level of microalbuminuria, none of Ames Multistix by visual reading and only 5 of 32 (15.6%) of those by reflectance photometer had false negative results. By visual reading, the sensitivity of Ames Multistix was increased from 68.1 to 100 per cent with the drop in specificity from 85.7 to 50.2 per cent. On the other hand, the sensitivity was increased from 37.4 to 84.4 per cent but the specificity was maintained if reflectance photometer was used. In conclusion, Ames Multistix was less sensitive than Micral-Test II in detection of urinary albumin concentration above 20 mg/L. At higher urinary albumin concentration above 60 mg/L which indicates a clinically significant microalbuminuria, the sensitivity of Ames Multistix was increased to 100 per cent. Ames Multistix which is much less expensive than Micral-Test II, can be used as the screening test for significant microalbuminuria in clinical practice particularly in cases having financial problems.

Postprandial plasma glucose: a good index of glycemic control in type 2 diabetic patients having near-normal fasting glucose levels.

To investigate the effect of postprandial plasma glucose (PG) concentrations on HbA1c levels in type 2 diabetic patients, we evaluated the relationship between HbA1c levels and postprandial PG concentrations after a meal tolerance test in 35 type 2 diabetic patients who had fasting PG concentrations persistently < 7.8 mmol/l and stable HbA1c levels. Two-hour postprandial PG concentrations were found to be more strongly correlated (r = 0.51) with HbA1c levels than 1-h postprandial PG (r = 0.35) and fasting PG (r = 0.46) concentrations. Patients whose HbA1c levels were high (HbA1c > or = 7%) had significantly higher 2-h postprandial PG concentrations and areas under the glucose curve than those whose HbA1c levels were lower (8.12+/-1.10 (SD) vs 6.70+/-2.22 mmol l(-1), P = 0.004 and 17.43+/-1.92 vs 15.58+/-3.26 mmol h(-1) l(-1), P = 0.02, respectively). Although fasting PG concentrations of patients with higher HbA1c levels were slightly higher, they did not differ significantly from those with lower HbA1c levels (6.21+/-0.89 vs 5.73+/-0.68 mmol l(-1)). Age, duration of diabetes, body mass index, serum C-peptide, both fasting and postprandial, did not differ between these two groups. This study suggests that postprandial hyperglycemia, particularly 2-h postprandial PG concentrations, is associated with high HbA1c levels in type 2 diabetic patients whose fasting PG levels were within normal or near-normal levels.

Clinical characteristics, and time course of pancreatic beta-cell function and glutamic acid decarboxylase antibodies in Thai patients with adult-onset Type 1 diabetes: distinction between patients of rapid- and slow-onset.

In order to study the clinical characteristics, time course of beta cell function and glutamic acid decarboxylase antibodies (GAD65Ab) in Thai patients with adult-onset Type 1 diabetes and to examine the distinctive features between patients with rapid-and slow-onset, 61 Thai patients with Type 1 diabetes who had age of disease onset at or after 20 years were studied. All patients were treated with insulin at the time of study and had fasting C-peptide levels +/-0.33 nmol/l. Twenty-six (42.6%) were in rapid-onset and 35 (57.4%) were in slow-onset groups. Fourty-four of 61 (70.5%) were male. About three-fourths had body mass index (BMI) < 19 kg/m2 at the time of insulin therapy. Only 7 of 61 (11.5%) patients had ketoacidosis at first presentation. Five patients had associated autoimmune thyroid disease and 10 (16.7%) patients had family history of diabetes in first-degree relatives. GAD65Ab was positive in 31 patients (50.8%); 10 (38.5%) were in rapid-onset and 21 (60.0%) were in slow-onset groups. GAD65Ab particularly of high levels were persistently elevated during 3-4 years follow-up period. The persistence of GAD65Ab were not associated with changes in fasting C-peptide levels. At the time of insulin dependency, there were no distinctive clinical features between rapid- and slow-onset patients except higher fasting C-peptide (0.08+/-0.08 vs. 0.14+/-0.10 nmol/l; p = 0.023) and GAD65Ab levels (19.6+/-17.4 vs. 46.1+/-49.7 U/ml; p = 0.036) in slow-onset patients. Fasting C-peptide levels of patients in the latter group were also demonstrated to be higher after 3-4 years of follow-up. In conclusion, most Thai patients with adult-onset Type 1 diabetes in this study were male and had significant degree of weight loss and lean BMI prior to insulin therapy. The presence of GAD65Ab did not predict clinical features or rate of beta cell loss. Patients in rapid-onset group had lower fasting C-peptide and GAD65Ab levels than those of slow-onset group which confirms the slower process of beta cell failure in the latter.

Effect of acarbose in treatment of type II diabetes mellitus: a double-blind, crossover, placebo-controlled trial.

This study evaluated the efficacy of acarbose in improvement of metabolic control in patients with fairly, well controlled non-insulin-dependent diabetes mellitus (NIDDM). Fifteen patients with mean age and duration of diabetes of 57.5 +/- 2.6 (SE) and 7.5 +/- 1.5 years, respectively were recruited and completed our study protocol. This study was a double-blind, crossover, placebo-controlled design consisting of two twelve-week treatments of acarbose and placebo separated by an eight-week washout period. Acarbose was effective in lowering of 1-hour and 2-hour postprandial plasma glucose from 251.7 +/- 10.7 and 205.3 +/- 9.1 mg/dl to 197.4 +/- 7.0 (p = 0.001) and 181.5 +/- 8.5 mg/dl (p = 0.03), respectively. Fasting plasma glucose was slightly decreased but without significant change, from 150.8 +/- 7.3 to 140.8 +/- 6.1 mg/dl (p = 0.07). Overall glycemic control tended to improve during the study period as indicated by the falling of HbA1c levels from 7.7 +/- 0.4 to 7.0 +/- 0.2 per cent (p = 0.05). Serum C-peptide both fasting and postprandial as well as serum lipids were not affected by acarbose. Almost half of the patients treated with acarbose had mild and tolerable gastrointestinal adverse effects. In conclusion, acarbose, as combined therapy with other oral hypoglycemic agents, was effective in improvement of glycemic control particularly postprandial hyperglycemia in fairly, well controlled NIDDM patients with mild and acceptable adverse effects.

Glutamic acid decarboxylase antibodies in non-insulin-dependent diabetes patients with secondary sulfonylurea failure in Thailand.

The objective of this study was to determine the frequency of glutamic acid decarboxylase antibody (GAD-Ab) in Thai non-insulin-dependent diabetes (NIDDM) patients who had secondary sulfonylurea failure. Sera were collected from 40 NIDDM patients, who had history of secondary failure to treatment with sulfonylurea, for analysis of fasting c-peptide and GAD-Ab. Both c-peptide and GAD-Ab were measured using radioimmunoassay method. Of 40 patients, ten (25.0%) were positive for GAD-Ab with a mean level of 59.9 U/ml (median 58.5, range 3.4-127). Patients with (GAD-Ab (+) had a significantly lower fasting c-peptide levels than those with GAD-Ab(-) albeit shorter duration of diabetes (0.21 +/- 0.19 (S.D.) versus 0.52 +/- 0.33 nmol/l; P = 0.003). Duration of treatment with sulfonylurea in patients with GAD-Ab (+) was also shorter (4.6 +/- 3.5 versus 10.4 +/- 5.5 years; P = 0.001). Age at onset of diabetes did not differ between these two groups. Among 40% of patients who had insulin deficiency (fasting c-peptide level < 0.33 nmol/1), GAD-Ab was present in half and these GAD-Ab(+) patients had significantly shorter duration of sulfonylurea treatment (3.3 +/- 2.3 versus 10.0 +/- 7.9 years; P = 0.018). In conclusion, the frequency of GAD-Ab in Thai NIDDM patients with secondary sulfonylurea failure in this study was 25%. Almost all GAD-Ab(+) patients had insulin deficiency and most had been initially treated with sulfonylurea for a few years before depending on insulin. This group of patients represents a slowly progressive type I or latent autoimmune diabetes in adult diabetic population.

Effect of pravastatin in treatment of hypercholesterolemia in non-insulin-dependent diabetes patients.

To evaluate the efficacy of pravastatin in treatment of hypercholesterolemia in non-insulin-dependent diabetes patients, a 6-month trial of once daily 10 mg-pravastatin was studied in 30 patients with fairly, well controlled non-insulin-dependent diabetes mellitus. For 27 patients who completed the study, serum total cholesterol and low-density lipoprotein cholesterol were significantly lower 16.7 +/- 2.3 and 20.2 +/- 3.3% from 286.7 +/- 5.9 and 198.6 +/- 7.2 mg/dl at before to 232.6 +/- 7.9 and 147.8 +/- 6.4 mg/dl at 4th week and 237.8 +/- 6.4 and 155.0 +/- 5.8 mg/dl at 24th week after treatment with pravastatin, respectively (P < 0.00001). Serum triglyceride level was decreased from 194.7 +/- 16.8 mg/dl to 175.0 +/- 16.8 mg/dl at 4th week and 176.6 +/- 14.1 mg/dl at 24th week and serum high-density lipoprotein cholesterol level was slightly increased from 45.4 +/- 2.8 mg/dl to 48.2 +/- 2.5 mg/dl at 4th week and 47.5 +/- 2.6 mg/dl at 24th week of pravastatin treatment, respectively (P > 0.05). There was no serious adverse effect except acute hepatitis in one patient who recovered spontaneously after drug withdrawal. Once daily 10 mg-pravastatin in effective in the treatment of hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus.

Hypoglycemia in sepsis: risk factors and clinical characteristics.

To determine risk factors for the development and clinical characteristics of hypoglycemia in patients with sepsis, a case-control study was performed in 52 case-patients who developed spontaneous hypoglycemia (plasma glucose < 50 mg/dl) during episodes of sepsis compared with 49 nondiabetic, control-patients who had sepsis as an immediate cause of death and did not develop hypoglycemia. The presence or absence of potential risk factors for the development of hypoglycemia which consisted of the state of starvation, malnutrition, renal insufficiency, acute or chronic liver disease and malignancy were evaluated in both groups as well as the clinical characteristics of hypoglycemia. The mean of the lowest plasma glucose levels in hypoglycemic patients was 23.4 +/- 14.9 (SD) mg/dl (range 3-47). One-third of patients were found having hypoglycemia since the time of arrival to the hospital. About 90 per cent had septic shock at the time of hypoglycemia. The mortality rate was 90 per cent; 80 per cent died within 48 hours after the first episode of hypoglycemia. Among those risk factors, starvation and liver disease were independently associated with the development of hypoglycemia with odd ratios of 6.38 (95% confidence interval 1.95-20.86; P = 0.002), and 3.59 (95% confidence interval 1.09-11.81; P = 0.035), respectively. In conclusion, hypoglycemia in patients with sepsis was associated with a grave prognosis. The risk of developing hypoglycemia increased significantly in patients who had been fasted for more than 24 hours or had acute or chronic liver disease at the time of sepsis.

Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM.

To test the hypothesis that the neuroendocrine (including autonomic) responses to hypoglycemia are dissociated from the symptomatic responses to hypoglycemia in insulin-dependent diabetes mellitus (IDDM) patients with hypoglycemia awareness and during reversal of hypoglycemia unawareness in IDDM, we used the hyperinsulinemic stepped hypoglycemic (5.0, 4.4, 3.9, 3.3, 2.8, and 2.2 mmol/l) clamp technique to quantitate these responses in nondiabetic control subjects and IDDM patients with hypoglycemia awareness and with hypoglycemia unawareness. The latter were restudied after 3 days, 3-4 weeks, and 3 months of scrupulous avoidance of iatrogenic hypoglycemia. At baseline, symptom responses were virtually nil in unaware patients (P = 0.0001 vs. nondiabetic); these were increased in aware patients (P = 0.0183 vs. nondiabetic). In contrast, several neuroendocrine responses were comparably reduced in both unaware and aware patients: epinephrine (P = 0.0222 and 0.0156), pancreatic polypeptide (P = 0.0004 and 0.0003), glucagon (P = 0.0112 and 0.0109), and cortisol (P = 0.0214 and 0.0450). In initially unaware patients, symptom responses increased (P = 0.0001) during avoidance of hypoglycemia. Demonstrable after 3 days, these were entirely normal after 3-4 weeks and 3 months. In contrast, none of the neuroendocrine responses increased. Thus, we conclude that several neuroendocrine responses to hypoglycemia (including the adrenomedullary and parasympathetic components of the autonomic response) can be dissociated from symptomatic responses in IDDM patients with hypoglycemia awareness and during reversal of hypoglycemia unawareness in IDDM. Avoidance of iatrogenic hypoglycemia sufficient to reverse the clinical syndrome of hypoglycemia unawareness did not reverse the key elements (deficient glucagon and epinephrine responses) of the clinical syndrome of defective glucose counterregulation. This implies that the mechanisms of hypoglycemia unawareness and of defective glucose counterregulation are, at least in part, different in IDDM.

Hypoglycemia-induced autonomic failure in IDDM is specific for stimulus of hypoglycemia and is not attributable to prior autonomic activation.

We hypothesized, first, that recent antecedent hypoglycemia causes reduced autonomic responses to subsequent hypoglycemia in patients with well-controlled insulin-dependent diabetes mellitus (IDDM) and that the reduced responses are specific for the stimulus of hypoglycemia while the responses to other stimuli are unaltered and, second, that reduced autonomic responses, specifically sympathochromaffin, so-induced are not simply the result of prior activation of the system. To test the first hypothesis, eight patients with IDDM, selected for HbA1c levels < 8.0% and the absence of classic diabetic autonomic neuropathy, were studied twice. On one occasion, clamped hypoglycemia (approximately 2.8 mM) was produced at 1400-1600 on days 2 and 3; on the other occasion clamped euglycemia (approximately 5.6 mM) was produced at those times. On both occasions, autonomic responses to hypoglycemia (approximately 2.8 mM) were determined the morning of day 3 and those to standing, exercise, and a formula meal the morning of day 4. Following afternoon hypoglycemia, 1) the adrenomedullary epinephrine (EPI) response to hypoglycemia was reduced (P = 0.0397) but that to standing, exercise, and a meal were unaltered; 2) the sympathetic neural norepinephrine (NE) response to standing and to exercise was unaltered; and 3) the partially parasympathetic neural-mediated pancreatic polypeptide response to a meal was unaltered. To test the second hypothesis, seven nondiabetic subjects were studied twice, once with cycle exercise (60% peak VO2 x 60 min) and once without exercise 90 min before clamped hypoglycemia (approximately 2.8 mM). Prior exercise had no effect on the EPI, NE, or pancreatic polypeptide responses to hypoglycemia. We conclude, first, that the phenomenon of hypoglycemia-associated autonomic failure can be induced in patients with well-controlled IDDM and is specific for the stimulus of hypoglycemia and, second, that this is not simply the result of prior activation of the system.

Thyroid function test in patient with acute-severe-nonthyroidal illnesses.

Patients with acute-severe-nonthyroidal illnesses had FT4 and T3 values below the normal range with the magnitude of change greater for T3 than FT4. Some patients had depressed and some had elevated TSH values. In the recovery phase, FT4 levels appeared to rise before T3 levels and TSH exhibited an exaggerated increase. These results are consistent with other studies which suggest that dysfunction of the hypothalamic-pituitary-thyroid axis may be associated with anomalous results for thyroid function test parameters in patients with acute-severe-nonthyroidal illnesses. This anomaly should be given due consideration when interpreting results of thyroid function test parameters in such patients.