bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Associated Conditions on Glycemic Control of NIDDM Patients
Authors: Ferrannini Eleuterio , Stern Michael P , Galvan Alfredo Quinones , Mitchell Braxton D , Haffner Steven M 
Published: March 2007

Objective
To assess the impact of associated conditions (obesity, dyslipidemia, and hypertension) on the glycemic control of non-insulin-dependent diabetes mellitus (NIDDM) patients under home-life conditions.

Research Design and Methods
We analyzed the metabolic data of 271 NIDDM patients (89% Mexican American) screened in a population-based survey (the San Antonio Heart Study).

Results
Obesity was present in 77% of the patients, hypertension in 23%, hypertriglyceridemia (serum triglycerides &gt;2.9 mM) in 23%, and hypercholesterolemia (serum total cholesterol &lt;6.5 mM) in 14%. Forty percent of the patients had two or more comorbid conditions. With the use of a multiple linear regression model, which was adjusted for age, sex, ethnicity, distribution of body fat (waist-hip ratio), plasma insulin, and treatment (of both diabetes and hypertension), we found that the presence of higher serum triglyceride concentrations was associated with significantly higher plasma glucose levels both in the fasting state (1.4 mM, P &lt;0.001) and 2 h after an oral glucose load (1.2 mM, P = 0.003). The presence of obesity, hypertension, or high serum cholesterol levels was not associated with significant changes in glycemic control. When the entire group was stratified by diabetes treatment (untreated n = 89, diet n = 75, oral agents n = 82, insulin n = 25) and after adjusting for age, sex, ethnicity, and waist-hip ratio, only fasting and 2-h plasma glucose and insulin concentrations were significantly different across treatment groups, with diet and oral agents being associated with higher fasting (P &lt;0.001) and postglucose (P &lt;0.005) plasma glucose levels and lower plasma insulin concentrations (P &lt;0.005) compared with newly diagnosed patients. Neither serum lipids nor blood pressure differed across treatment.

Conclusions
In NIDDM patients under home-life conditions, higher serum triglycerides are associated with higher fasting and postglucose hyperglycemia regardless of antidiabetic treatment. The presence of obesity, hypertension, or high serum cholesterol levels is not associated with significant changes in glycemic control.
Dichloroacetate
Authors: Stacpoole Peter W , Greene Yvonne J 
Published: March 2007

Dichloroacetate (DCA) represents a potentially novel class of oral antidiabetic agents that reduce blood glucose and lipids without stimulating insulin secretion. DCA reduces blood glucose by inhibiting hepatic glucose synthesis and stimulating glucose clearance and use by peripheral tissues. A major site of action of the drug is pyruvate dehydrogenase (PDH), the rate-limiting enzyme of aerobic glucose oxidation. Stimulation of PDH by DCA increases peripheral oxidation of alanine and lactate, thereby interrupting the Cori and alanine cycles and reducing the availability of three-carbon precursors for gluconeogenesis. In experimental models of ketosis, DCA reduces ketonemia and ketonuria while significantly lowering blood glucose.
DCA inhibits hepatic triglyceride and cholesterol biosynthesis. Short-term studies in patients with non-insulin-dependent diabetes have demonstrated a capacity of the drug to markedly reduce circulating a very-low-density lipoprotein cholesterol and triglyceride concentrations. In genetic models of insulin-dependent diabetes, oral administration of DCA significantly reduces insulin requirements and blood levels of glucose and triglycerides.
Several derivatives of DCA have been synthesized and found to have biological activity in animals. Further work is required to determine whether DCA and its analogues may be safe and effective agents for chronic treatment of the carbohydrate and lipid abnormalities of human diabetes.
Homogeneity in Pattern of Decline of β-Cell Function in IDDM: Prospective study of 204 consecutive cases followed for 7.4 yr
Authors: Snorgaard Ole , Lassen Lassen H , Binder Christian 
Published: March 2007

OBJECTIVE
To study the natural history of β-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any.

RESEARCH DESIGN AND METHODS
A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6–9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104–135 wk). Then, postprandial C-peptide was measured.

RESULTS
Fasting C-peptide was 0.17 nM (range 0.11–0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06–0.48 nM/yr) to a peak of 0.28 nM (range 0.23–0.34 nM/yr) after 25 wk (range 12–39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05–0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02–0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects &gt; 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences.

CONCLUSIONS
No major heterogeneity exists in the pattern of decline of β-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.
Granulocytes and Three-Phase Bone Scintigraphy for Differentiation of Diabetic Gangrene with and Without Osteomyelitis
Authors: Ritter Michael M , Richter Werner O , Leinsinger Gerda , Kirsch Carl Martin , Schwandt Peter 
Published: March 2007

OBJECTIVE
In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful.

RESEARCH DESIGN AND METHODS
Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123 I-labeled antibodies against granulocytes (n = 11).

RESULTS
Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods.

CONCLUSIONS
In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method.
The Effect of Glyburide on β-Cell Sensitivity to Glucose-Dependent Insulinotropic Polypeptide
Authors: Meneilly Graydon S , Bryer-Ash Michael , Elahi Dariush 
Published: March 2007

Objective— To assess whether treatment with glyburide alters β-cell sensitivity to GIP in NIDDM patients.
Research Design and Methods— We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the clamp, GIP was infused in a primed continuous manner at a rate of 2 pmol·kg−1·min−1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated.
Results— In response to treatment, a decrease in fasting glucose and an increase in weight was observed (12.8 ± 1.8 vs. 8.5 ± 0.8 mM and 74.3 ± 6.3 vs. 76.1 ± 6.3 kg, respectively, P &lt; 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 ± 2.1 vs. 12.6 ± 6.9 mM, P &lt;0.05; 161 ± 47 vs. 242 ± 60 pM, P &lt; 0.05; and 199 ± 22 vs. 219 ± 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 ± 1.3 vs. 18.3 ± 1.3 mM and 302 ± 59 vs. 298 ± 37 pM, respectively). The 90b–120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 ± 37 vs. 283 ± 80 pM, P &lt; 0.05) reflecting increased β-cell responses to GIP.
Conclusions— We conclude that glyburide enhances β-cell sensitivity to GIP.
Decrease of Glomerular Hyperfiltration in Short-Term Diabetic Adolescents Without Microalbuminuria
Authors: Bognetti Emilio , Meschi Franco , Bonfanti Riccardo , Gianolli Luigi , Chiumello Giuseppe 
Published: March 2007

Objective— This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE.
Research Design and Methods— The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 ± 10.4 mo of follow-up.
Results— GFR decreased in the two groups but Δ GFR of patients with glomerular hyperfiltration was greater than Δ GFR of patients with normal GFR (0.83 ± 0.55 vs. 0.28 ± 0.63 ml·min−1·mo−1; P &lt; 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P &lt; 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up.
Conclusions— Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.
Determinants of Clinical Remission in Recent-Onset IDDM
Authors: Hramiak Irene M , Dupre John , Finegood Diane T 
Published: March 2007

Objective— To assess the relationship of SI and insulin secretion (C-peptide levels) to remission status in recent-onset IDDM.
Research Design and Methods— We followed 22 newly diagnosed patients, of whom 16 received immunomodulatory treatment with low-dose (5 mg·kg−1·day−1) CsA and/or short-term (72 h) methylprednisolone and 6 received standard insulin treatment, at 3-mo intervals for 12 mo. Insulin secretion was assessed by C-peptide levels and AIRglu, which was determined as the area under the insulin response curve, above the fasting level, from 0–10 min after a 0.3 g·kg−1·i.v. glucose xbolus. SI was assessed by the minimal model technique applied to a frequently sampled IVGTT. Clinical remission was defined in those patients who maintained normal range GHb and capillary blood glucose levels &lt;7.8 mM premeal without insulin therapy for a minimum of 14 days.
Results— The rate of clinical remission was not different with immunomodulatory treatment; nor were the metabolic parameters of plasma C-peptide levels, AIRglu, and S1 different in the treatment groups. The mean plasma C-peptide level improved significantly at 3 mo and was maintained to 12 mo. AIRglu was grossly subnormal throughout, but a significant improvement was seen at 3 and 6 mo. Mean SI was normalized at 3 and 6 mo but not maintained beyond 9 mo. The maximum rate of clinical remission was seen at 6 mo.
Conclusions— Clinical remission in recent-onset IDDM patients is associated with improvement in both insulin secretion and SI. Although the improvement in basal C-peptide persisted, AIRglu increased only transiently and declined as loss of remission occurred in most patients. Loss of remission to an insulin-requiring state is associated with a decrease in SI.
Lower-Extremity Amputations in Diabetic and Nondiabetic Patients: A population-based study in eastern Finland
Authors: Siitonen Onni I , Niskanen Leo K , Laakso Markku , Siitonen Jukka T , Pyörälä Kalevi 
Published: March 2007

Objective— To study the incidence of LEAs attributable to PVD in diabetic and nondiabetic patients. The age at first amputation, the level of amputation, the number of reamputations, and survival after amputation also were examined in the study populations.
Research Design and Methods— This retrospective study was based on a population of 253,000 inhabitants in eastern Finland. All patients with their first LEA performed during the period from 1 January 1978 to 31 December 1984 were identified from the registers of operation theaters in the study area. Furthermore, patient records and death certificates were reviewed. Amputations attributable to causes other than evident atherosclerotic vascular disease were excluded.
Results— Altogether, 477 patients (85 diabetic men, 127 nondiabetic men, 169 diabetic women, and 96 nondiabetic women) were identified. The overall LEA rate was 26.9/100,000 per yr, and the incidence increased strongly with age in both diabetic and nondiabetic patients. The age-adjusted amputation incidence per yr was 349.1/100,000 for diabetic men, 33.9/100,000 for nondiabetic men, 239.4/100,000 for diabetic women, and 17.2/100,000 for nondiabetic women. The proportion of peripheral (toe, leg) amputations was markedly higher in diabetic patients who also tended to have more reamputations during the follow-up than did nondiabetic subjects. The diabetic status per se was a statistically significant risk factor for mortality in women, but not in men.
Conclusions— Diabetic men and women had a 10.3- and 13.8-fold higher risk, respectively, for LEA.
Diabetes and Plasma Lipoproteins in Native Americans: Studies of the Pima Indians
Authors: Howard Barbara V 
Published: March 2007

OBJECTIVE– To determine the effects of diabetes on plasma lipoproteins in Pima Indians, to identify metabolic determinants of these differences, and to examine the effects of various modes of diabetes therapy.
RESEARCH DESIGN AND METHODS— A series of studies was performed including a population survey of lipoprotein concentrations, kinetic studies of VLDL and LDL metabolism, and studies of the effects of weight loss, sulfonylureas, and high carbohydrate diets.
RESULTS— Population data established that diabetes was consistently associated with elevations in total and VLDL TGs and decreases in HDL cholesterol. Metabolic studies indicated multiple alterations in VLDL metabolism induced by NIDDM, including overproduction of VLDL TG, impaired clearance of VLDL TG and apoB, and decreases in adipose tissue lipoprotein lipase. Although changes in LDL concentrations accompanying NIDDM were minimal, the clearance of LDL appeared to be impaired and a higher proportion of VLDL was metabolized without conversion to LDL. There were significant changes in the flux of particles to the LDL compartment. Total and VLDL TG concentrations were found to be inversely related to rates of insulin-mediated glucose disposal, and HDL cholesterol concentrations were positively related to glucose disposal. These relationships between lipoproteins and insulin action were independent of adiposity and insulin, suggesting that insulin resistance may be involved with diabetes-induced changes in VLDL and HDL. Weight loss was associated with decreases in total and VLDL TG, decreases in total and LDL cholesterol, and improvements in the ratio of HDL to LDL cholesterol. Sulfonylurea therapy was associated with lower total and VLDL TGs and lower LDL cholesterol, but little change in HDL. Substitution of complex carbohydrates for saturated fat in the diet showed consistent and significant decreases in total and LDL cholesterol, no decreases in HDL cholesterol, or elevation of total or VLDL TG.
CONCLUSIONS— Studies suggest that there are multiple changes in plasma lipoproteins accompanying NIDDM in Pima Indians, but that many of these may be reversed by current modes of hypoglycemic therapy.
Insulin Therapy and Weight Change in Native-American NIDDM patients
Authors: Hickey Martin E , Hall Terri R 
Published: March 2007

OBJECTIVE— To determine whether NIDDM patients exposed to insulin therapy in a clinical setting gain weight.
RESEARCH DESIGN AND METHODS— This study, an historical cohort chart review, was conducted at the IHS clinic on the Navajo Reservation in Northern Arizona. We studied 27 Native Americans with NIDDM and 102 Native-American nondiabetic control subjects.
RESULTS— Insulin therapy consisting of a mean of 105 U/day was associated with a mean weight gain of 3.0 ± 2.2 kg/yr. When insulin was discontinued or decreased, a mean weight loss of 5.2 ± 2.7 kg/yr was observed in the same patients. No significant weight gain was noted in 102 nondiabetic control subjects, nor in 20 of 27 insulin-treated patients given oral hypoglycemic agents before initial insulin therapy.
CONCLUSIONS— Insulin therapy appeared to be associated with weight gain in this group of NIDDM patients. This suggests that observations for weight gain be undertaken when treating NIDDM patients with insulin, because it may exacerbate the underlying pathophysiology of the disease.
Improvement of Diabetic Control and Acceptability of a Three-Injection Insulin Regimen in Diabetic Adolescents: A multicenter controlled study
Authors: Bougnères P F , Landais P , Mairesse A M , Jais J P , Jos J , Peyraud J , Wieliczko M C , Chavoix P , Garandeau P , Asensi D , Ythier H , Rouland V , Mazoyer T , Leturcq F , Raynaud E 
Published: March 2007

Objective— To compare the effectiveness and acceptability of a three-injection insulin regimen with the conventional two-injection therapy in an unselected population of diabetic adolescents.
Research Design and Methods— Some 205 patients aged 10–18 yr with IDDM, who were previously treated with two daily insulin injections, were included without any selection into a randomized trial. They were either switched to three (regular prebreakfast, regular prelunch, and [regular + ultralente] predinner) or remained on two ([regular + intermediary] prebreakfast and predinner) subcutaneous injections. They were evaluated after 1 yr of treatment. The major criteria of outcome of efficacy were the concentration of GHb, the frequency of severe hypoglycemia and DKA, and body weight.
Results— Of the patients, 82% accepted the three-injection regimen, and 83% accepted the two-injection regimen. At entry into the trial, no significant differences appeared between the two treatment groups nor among patients refusing the allocated regimen. Significant explanatory variables predicting initial diabetes control were duration of disease and adherence to diet. GHb, decreased from 9.8 ± 0.1 to 9.3 ± 0.2% (P &lt; 0.05) in the three-injection group, whereas it increased from 9.5 ± 0.3 to 9.8 ± 0.3% (P &lt; 0.05) in the two-injection group, resulting in a modest (0.75%) but significant difference (P &lt; 0.05) between GHb change in the two groups. The difference reached 1.4% (P &lt; 0.0002) in patients with GHb &gt; 11.2% at entry. The frequency of hypoglycemia and DKA was similar in the two groups. None of the parameters known to potentially influence glycemic control changed during the trial, and, therefore, the improvement of GHb could be attributed to the pattern of daily insulin distribution per se.
Conclusions— In the general diabetic adolescent population, the efficacy of a three-injection regimen is somewhat superior to that of a conventional two-injection regimen, particularly in patients previously poorly controlled. The acceptability of this regimen being excellent, its increased use should be considered in this age-group.
Neurophysiological Impairments in IDDM Patients During Euglycemia and Hypoglycemia
Authors: Lingenfelser Thomas , Buettner Ulrich W , Sommerwerck Urte , Renn Walter , Eggstein Manfred , Jakober Bernhard 
Published: March 2007

OBJECTIVE
To test the hypothesis that latencies of evoked potentials in IDDM patients are delayed compared with healthy control subjects during euglycemia, and that insulin-induced hypoglycemia causes further latency delays of evoked potentials to occur.

RESEARCH DESIGN AND METHODS
We recruited 23 IDDM patients (27.9 ± 1.6 yr of age, HbA1c 6.7 ± 0.3%, without sensory or autonomic neuropathy) and 26 unequivocally healthy subjects who were carefully matched for sex, age, and body mass index to serve as the control group (18 men and 8 women, 28.4 ± 1.6 yr of age, 22.6 ± 0.7 kg/m2), for a controlled, prospective study. Sequential euglycemichypoglycemic clamps were performed with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' and healthy control subjects' neurophysiological functions were evaluated. The methodological armamentarium included the measurement of brainstem auditory, middle-latency auditory, and somatosensory evoked potentials that assessed conduction velocity in corresponding neural structures and information processing in the midbrain and auditory cortex.

RESULTS
Multiple analysis of variance revealed a significant overall difference of brainstem auditory evoked potential latencies during euglycemia between the study group and healthy control group (F = 3.41, P &lt; 0.03), which was mainly attributable to latency delays of wave III (F = 6.60, P &lt; 0.02), V (F = 9.19, P &lt; 0.01), and interpeak latency 1-V (F = 2.82, P &lt; 0.07). Repeated analysis of variance measures detected a significant latency delay of the major wave Pa of the middle-latency auditory evoked potentials during hypoglycemia (F = 4.4, P &lt; 0.02), which rapidly returned to normal after reinstitution of euglycemia.

CONCLUSIONS
In IDDM patients, chronic, structural CNS changes already appear at the brainstem level during euglycemia. Functional, reversible CNS changes, however, seem to emerge during acute deviation from glucose homeostasis in more rostral brain regions.