bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric Myoelectrical Activity in Patients With Diabetes: Role of glucose control and autonomic nerve function
Authors: Kawagishi Takahiko , Nishizawa Yoshiki , Emoto Masanori , Maekawa Kiyoshi , Okuno Yasuhisa , Taniwaki Hiromichi , Inaba Masaaki , Ishimura Eiji , Morii Hirotoshi
Published: March 2007

OBJECTIVE

Gastric myoelectrical activity was studied in diabetic patients using electrogastrography (EGG) to elucidate the relationship between glucose control, diabetic autonomic neuropathy (AN), and gastrointestinal motility.

RESEARCH DESIGN AND METHODS

Cutaneous EGG was recorded during 1 h of fasting and 1 h after the ingestion of a standard meal in 57 diabetic patients and 10 healthy subjects. EGG was measured in 12 diabetic patients after glycemic control for 4 weeks. Diabetic patients were also studied with respect to the presence of gastrointestinal symptoms and AN.

RESULTS

The percentage of dominant electrical frequency (DF) in normal range (the percentage ratio between the power at 2.4–3.6 cycles/min [cpm] and at 1–10 cpm) was significantly lower in patients with AN than in either the control subjects or the patients without AN (P < 0.01). The dominant frequency instability coefficient (DFIC) was significantly higher in patients with and without AN than in the control subjects (P < 0.01). The postprandial-to-fasting power ratio (PR) was the lowest in patients with AN (P < 0.01). Multiple regression analysis revealed that HbA1c levels were independently associated with the DFIC (R2 = 0.099, P = 0.0170) and that AN and HbA1c levels were independently associated with the PR (R2 = 0.378, P < 0.0001) in diabetic patients. The percentage of normal DF increased and the DFIC decreased significantly after glycemic control in 12 diabetic patients (P = 0.0409; P = 0.0096, respectively).

CONCLUSIONS

There appears to be an association between improvement in gastric myoelectrical activity and autonomic nerve function. Abnormalities of gastric myoelectrical activity may be partly ameliorated via the improvement of autonomic nerve function, which accompanies glycemic control.
White Coat Hypertension in NIDDM Patients With and Without Incipient and Overt Diabetic Nephropathy
Authors: Nielsen Flemming S , Gæde Pernille , Vedel Pernille , Pedersen Oluf , Parving Hans-Henrik
Published: March 2007

OBJECTIVE

Early data have suggested a high prevalence of white coat hypertension (∼ 50%) in NIDDM patients. To study this phenomenon further, we determined the prevalence of white coat hypertension in NIDDM patients with normo- or microalbuminuria or with diabetic nephropathy.

RESEARCH DESIGN AND METHODS

Three groups of hypertensive NIDDM patients (repeated clinic blood pressure > 140/90 mmHg or antihypertensive treatment) attending the Steno Diabetes Center were investigated in a cross-sectional study. Group 1 had normoalbuminuria (a urinary albumin excretion [UAE] rate < 30 mg/24 h, n = 30, age 61 ± 7 [mean ± SD] years, 20 men), group 2 had microalbuminuria (UAE rate 30–300 mg/24 h, n = 51, age 55 ± 7 years, 35 men), and group 3 had diabetic nephropathy (UAE rate > 300 mg/24h, n = 47, 62 ± 7 years, 36 men). If given, all previous antihypertensive medication was withdrawn at least 2 weeks before the study (48%). The prevalence of white coat hypertension (clinic hypertension with normal blood pressure values at home) was determined by comparison of clinic blood pressure (Hawksley Random sphygmomanometer) and the ambulatory daytime (7:00 A.M. to 11:00 P.M.) blood pressure (A&D TM2420). By applying established criteria, white coat hypertension was confirmed if daytime blood pressure was < 135/85 mmHg.

RESULTS

The clinic blood pressure was 155/86 (SE 3/2) mmHg, 156/89 (2/1) mmHg, and 171/90 (3/2) mmHg in group 1, 2, and 3, respectively (P < 0.05 comparing group 3 with groups 1 and 2). The prevalence of white coat hypertension was significantly higher in group 1 as compared with groups 2 and 3, 23% (95% CI 10–42) vs. 8% (2–19) and 9% (2–20) (P < 0.05), with no difference between the latter two groups.

CONCLUSIONS

The prevalence of white coat hypertension in normoalbuminuric NIDDM patients resembles that observed in nondiabetic subjects with essential hypertension, whereas the prevalence is significantly lower in NIDDM patients with incipient or overt diabetic nephropathy, suggesting a difference between primary and secondary hypertension.
Deficient Counterregulation: A Possible Risk Factor for Excessive Fetal Growth in IDDM Pregnancies
Authors: Rosenn Barak M , Miodovnik Menachem , Khoury Jane C , Siddiqi Tariq A
Published: March 2007

OBJECTIVE

The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia.

RESEARCH DESIGN AND METHODS

Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24–28 and at 32–34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations.

RESULTS

All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244–764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05).

CONCLUSIONS

Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.
Perspectives in Pancreatic and Islet Cell Transplantation for the Therapy of IDDM
Authors: Calafiore Riccardo
Published: March 2007

Endocrine pancreas transplantation could provide an ideal solution to the problem posed by IDDM. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more “traumatizing” whole-pancreas transplantation, but only if the pending technical problems are fully surmounted. Combined pancreas/kidney (either simultaneous pancreas/kidney [SPK] or pancreas after kidney [PAK]) transplantation, under general immunosuppression, in IDDM patients also suffering from end-stage renal disease (ESRD) is a procedure that may be worth pursuing in selected cases. However, there are still quite serious reservations about the scaled-up applicability of pancreas transplant alone (PTA) in patients with “brittle” IDDM; major restrictions are not only the necessity of pharmacological immunosuppression, but also the lower functional performance of PTA, especially as compared with SPK grafting. In terms of islets, as problems of human islet yield and purity are gradually being overcome, the problem of islet graft-directed immune destruction hampers the success of ongoing clinical trials in IDDM patients. The invariable requirement of general immunosuppression affects pancreatic as much as islet grafts, although a number of alternative, yet experimental, immunoprotection strategies in progress might suit islets better than they would whole organs. Another issue concerns the relative inadequacy of cadaveric donor organ availability, the requirements of which are more stringent for islets because of the persistent variability of islet cell yield per organ. Tremendous experimental efforts are in progress to create xenogeneic porcine/bovine islets and, perhaps over a longer period of time, human/nonhuman engineered insulin-producing cells suitable for graft within special immunoisolation barrier membranes.
Erythromycin Derivative Improves Gastric Emptying and Insulin Requirement in Diabetic Patients With Gastroparesis
Authors: Ishii Masataka , Nakamura Teruo , Kasai Fukio , Baba Tsuneharu , Takebe Kazuo
Published: March 2007

OBJECTIVE

To evaluate the effect of the erythromycin derivative EM523L on gastric emptying and postprandial insulin requirement in insulin-dependent diabetic patients with severe gastroparesis.

RESEARCH DESIGN AND METHODS

In six IDDM patients with severe gastroparesis (two men and four women, mean age 44.5 years [range 36–53]), the insulin infusion pattern during feedback control with an artificial endocrine pancreas device (Biostator) after intake of a test meal, the retention rate of residual isotope (99mTc-labelled Sn-colloid) in the stomach, and the time-concentration curve of plasma acetaminophen as the marker for liquid emptying were studied with EM523L or a control placebo

RESULTS

Time courses of insulin infusion rates peaked within 120 min after intake of the test meal in the EM523L phase, whereas no apparent peak rates were observed in the control phase. The total amount of insulin required in the first 90 min postprandial was significantly greater in the EM523L phase than in the control phase. EM523L significantly decreased the residual isotope ratio in the stomach at ≥50 min postprandial and increased the plasma acetaminophen concentrations at 30–120 min postprandial, compared with respective values in the control phase.

CONCLUSIONS

Preliminary results obtained from a small number of patients suggest that EM523L or erythromycin analogs, which have agonistic activity to motilin receptors as well as no antibacterial effect, may be useful to accelerate gastric emptying and improve insulin requirement patterns, thereby establishing more stable glycemic control.
Long-Term Hyperglycemia Is Related to Peripheral Nerve Changes at a Diabetes Duration of 4 years
Authors: Allen Catherine , Shen Guanghong , Palta Mari , Lotz Barend , Jacobson Richard , D'Alessio Donn ,   For the Wisconsin Diabetes Registry
Published: March 2007

OBJECTIVE

To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort.

RESEARCH DESIGN AND METHODS

A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored.

RESULTS

GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (β = 0.17 male subjects, β = −0.01 female subjects; P < 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (β = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex.

CONCLUSIONS

Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.
Clinical Characteristics of Japanese Men With Glucokinase Gene β-cell Promoter Variant
Authors: Yamada Kentaro , Yuan Xiaohong , Ishiyama Satomi , Ichikawa Fumi , Koyama Ken-Ichi , Koyanagi Atsuko , Koyama Wasaku , Nonaka Kyohei
Published: March 2007

OBJECTIVE

To study the association between a variant at the position of −30 of β-cell-specific promoter of the glucokinase gene and glucose tolerance in the Japanese general population and to assess the clinical characteristics of subjects with the variant.

RESEARCH DESIGN AND METHODS

The genotype of 657 Japanese men aged 51.0 ± 8.8 years (mean ± SD) was analyzed by an allele-specific assay using polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

The variant allele frequency was 0.188 in subjects with normal glucose tolerance, 0.211 in subjects with impaired glucose tolerance, and 0.176 in diabetic subjects. In subjects with fasting plasma glucose levels <140 mg/dl, homozygous subjects for the promoter variant had significantly higher plasma glucose levels 60 min after oral glucose administration when compared with subjects without the variant allele. A cross-sectional analysis showed age-related elevation of basal glucose levels only in subjects without the promoter variant. Individuals heterozygous for the variant had significantly lower levels of HDL cholesterol than normal subjects. HDL cholesterol values were lower in homozygous people than in normal and heterozygous subjects, although the differences were not statistically significant.

CONCLUSIONS

The β-cell promoter variant in homozygous state was associated with impaired glucose tolerance, but not with diabetes, and low HDL cholesterol levels in Japanese men. It is unlikely that the glucose intolerance associated with the promoter variant is progressive with age.
Proinsulin, Intact Insulin, and Fibrinolytic Variables and Fibrinogen in Healthy Subjects: A population study
Authors: Eliasson Mats , Røder Michael E , Dinesen Bo , Evrin Per-Eric , Lindahl Bernt
Published: March 2007

OBJECTIVE

As high serum insulin predicts impaired fibrinolysis and proinsulin reacts in most conventional insulin assays, we hypothesized that proinsulin could link low fibrinolytic activity and hyperinsulinemic conditions.

RESEARCH DESIGN AND METHODS

We explored the relationship between fibrinolysis and plasma fibrinogen on the one hand and specific insulin and proinsulin on the other, in a healthy population sample of 165 men and women, 25–74 years of age, from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Study. Specific insulin and proinsulin were measured by enzyme-linked immunosorbent assay. Partial correlation coefficients, adjusted for age and sex, were calculated.

RESULTS

Plasma fibrinogen levels were related to insulin (r = 0.25, P < 0.01) and proinsulin (r = 0.29, P < 0.001), as was plasminogen activator inhibitor (PAI)-1 activity (r = 0.36 and r = 0.29, respectively; P < 0.001). Tissue Plasminogen activator (tPA) activity correlated inversely to insulin (r = −0.35, P < 0.001) and proinsulin (r = −0.36, P < 0.001). In a multivariate analysis taking also smoking and anthropometric and metabolic measurements into account, fasting proinsulin was a significant predictor of high plasma fibrinogen level. Insulin and proinsulin levels were not related to tPA activity. High levels of postload insulin, triglycerides, and diastolic blood pressure, but not proinsulin, predicted high PAI-l activity.

CONCLUSIONS

In a healthy population, the relationship previously described between high insulin levels and impaired fibrinolysis is not attributable to confounding from proinsulin. Elevated proinsulin levels are associated with high fibrinogen levels.
The Effect of Short Periods of Caloric Restriction on Weight Loss and Glycemic Control in Type 2 Diabetes
Authors: Williams Katherine V , Mullen Monica L , Kelley David E , Wing Rena R
Published: March 2007

OBJECTIVE

To determine whether an intermittent very-low-calorie diet (VLCD) improves weight loss and glycemic control more than moderate caloric restriction alone.

RESEARCH DESIGN AND METHODS

Individuals with type 2 diabetes (n = 54) who were ≥ 20% over ideal body weight participated in a 20-week behavioral weight control program. Subjects were randomized to either a standard behavioral therapy (SBT) group or to one of two VLCD groups. SBT subjects received a 1,500−1,800 kcal/day diet throughout. Both VLCD groups followed a VLCD for 5 consecutive days during week 2, followed by either intermittent VLCD therapy for 1 day/week for 15 weeks (1-day) or for 5 consecutive days every 5 weeks (5-day), with a 1,500−1,800 kcal/day diet at other times.

RESULTS

Both VLCD groups lost more weight than the SBT group over the 20 weeks (P = 0.04). Although the groups did not differ in fasting plasma glucose (FPG) changes at 20 weeks, more subjects in the 5-day group attained a normal HbA1c when compared with the SBT group (P = 0.04). This benefit was independent of the effects of weight loss. The best predictor of overall change in FPG and HbA1c was the FPG response during the first 3 weeks of the program.

CONCLUSIONS

Periodic VLCDs improved weight loss in diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed particularly promising, because more subjects in this group attained a normal HbA1c. Moreover, the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks, and it was a better predictor of the 20-week response than initial or overall weight loss.
The STOP-NIDDM Trial: An international study on the efficacy of an α-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data
Authors: Chiasson Jean-Louis , Gomis Roman , Hanefeld Markolf , Josse Robert G , Karasik Avraham , Laakso Markku ,   The Stop-Niddm Trial Research Group
Published: March 2007

OBJECTIVE

To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the α-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration ≥5.6 mmol/l were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile.

RESULTS

Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study. This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI ≥27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes.

CONCLUSIONS

Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.
Influence of puberty on endothelial dysfunction and oxidative stress in young patients with type 1 diabetes.
Authors: Elhadd T A , Khan F , Kirk G , McLaren M , Newton R W , Greene S A , Belch J J
Published: March 2007

OBJECTIVE: To examine the influence of puberty on endothelial dysfunction and oxidative stress in children and young people with type 1 diabetes. RESEARCH DESIGN AND METHODS: There were 51 young patients with type 1 diabetes, including 12 prepubertal children, 16 adolescents, and 23 young adults who had no clinical diabetic angiopathy, studied; none had microalbuminuria. The three groups were matched for glycemic control, and systolic and diastolic blood pressures and cholesterol levels were not significantly different between the groups. Endothelium-dependent vasodilatation was assessed by laser Doppler flowmetry after iontophoresis of acetylcholine (ACh) to the skin of the dorsum of the right foot. Soluble E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), plasma thiol (PSH), red cell glutathione (GSH), and red cell superoxide dismutase (SOD) were measured in blood samples obtained in the early morning. RESULTS: Skin vascular responses to ACh were significantly reduced in the young adult group compared with the prepubertal group (P < 0.05, analysis of variance). The levels of soluble ICAM-1 and E-selectin were significantly higher in the adolescent group compared with the young adult group: 338 (267-415) and 89 (64-106) ng/ml (median [interquartile range]), respectively, versus 255 (222-284) and 58 (54-71) ng/ml (P < 0.01 and P < 0.005, Mann-Whitney U test). SOD levels were significantly higher in the prepubertal group at 250 (238-282) micro/ml, when compared with the adolescent, 217 (171-249) micro/ml (P < 0.04), and young adult, 217 (157-244) micro/ml (P < 0.02), groups. GSH tended to be lower in the adolescent group, 1,192 (1,047-1,367) micromol/l, when compared with the young adults, 1,286 (1,145-1,525) pmol/l, and levels of vWF tended to be higher in the adolescent group, but these failed to reach statistical significance (both P = 0.09). PSH was not different between the three groups. CONCLUSIONS: These results suggest that puberty modulates endothelial function and antioxidant mechanisms in childhood diabetes, which may have implications for therapy and intervention.
The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes.
Authors: Berg T J , Clausen J T , Torjesen P A , Dahl-Jørgensen K , Bangstad H J , Hanssen K F
Published: March 2007

OBJECTIVE: To investigate whether children and adolescents with type 1 diabetes have increased serum levels of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) at an early stage of the disease. RESEARCH DESIGN AND METHODS: The serum levels of CML in 38 patients with type 1 diabetes aged 14+/-3.2 (mean+/-SD) years were compared with those in 26 control subjects aged 16+/-1.7 years. The mean duration of diabetes was 5+/-4.7 years, ranging from 0.5 to 15 years. The mean levels of HbA1c were 10.3+/-2.5% in the patient group. The serum levels of CML were measured using a monoclonal anti-CML antibody in a fluoremetric immunoassay. Serum protein levels of advanced glycation end products (AGEs) were assayed using a polyclonal antibody from rabbit immunized with AGE-RNase (pAGE). RESULTS: The serum levels of CML and pAGE were significantly increased in the patient group versus the control group: 1.08 (0.45-2.97) U/ml CML (median 10-90 percentiles) vs. 0.70 (0.36-1.79) U/ml CML, P < 0.03, and 6.6 (5.1-9.9) U/ml pAGE vs. 5.5 (3.7-8.2) U/ml AGEs, P < 0.01. A significant relationship between CML and pAGE was found in the IDDM group, r = 0.76, P < 0.001. The CML levels were not associated with the HbAlc levels (n = 23, r = -0.02, NS), cholesterol levels (n = 21, r = 0.07, NS), age, sex, or diabetes duration. CONCLUSIONS: Serum levels of CML are increased in patients with type 1 diabetes. This increase precedes the development of micro- and macrovascular complications.
Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.
Authors: Rossing K , Jacobsen P , Rossing P , Lauritzen E , Lund-Andersen H , Parving H H
Published: March 2007

OBJECTIVE: To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. RESEARCH DESIGN AND METHODS: All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). RESULTS: Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. CONCLUSIONS: The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.
Efficacy and Safety of Acarbose in Metformin-Treated Patients With Type 2 Diabetes
Authors: Rosenstock Julio , Brown Ann , Fischer Jerome , Jain Adesh , Littlejohn Thomas , Nadeau Dan , Sussman Allen , Taylor Terry , Krol Alice , Magner James
Published: March 2007

OBJECTIVE

To demonstrate the efficacy, tolerability, and safety of acarbosecompared with placebo in patients with type 2 diabetes inadequatelycontrolled with diet and metformin (2,000 or 2,500 mg/day in divideddoses).

RESEARCH DESIGN AND METHODS

This study had a multicenter randomized double-blind placebo-controlled parallel-group comparison design. The trial lasted 31 weeks and consisted of a 1-week screening period, a 6-week placebo pretreatment period, and a 24-week period of acarbose or placebo, with a forced titration from 25–50 mg t.i.d. and a titration of 50–100 mg tid that was based on glucose control. The primary efficacy variable wasthe mean change from baseline in HbAlc. Secondary efficacy variables included mean changes from baseline in fasting and postprandial plasma glucose, serum insulin, and triglyceride levels.

RESULTS

The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbAlc of 0.65%. There were statistically significant reductions in fasting and postprandial plasma glucose and serum insulin levels compared with placebo. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. No significant differences in liver transaminase elevations were observed between patients treated with acarbose and those treated with placebo.

CONCLUSIONS

The results of this study demonstrate that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with metformin and diet is safe and generally well tolerated and that it significantly lowers HbAlc and fasting and postprandial glucoseand insulin levels.
Biological Variation of Glycated Hemoglobin: Implications for diabetes screening and monitoring
Authors: Kilpatrick Eric S , Maylor Paul W , Keevil Brian G
Published: March 2007

OBJECTIVE

To assess the inherent potential of glycated hemoglobin as a screening test for type 2 diabetes by determining the biological variation in nondiabetic subjects.

RESEARCH DESIGN AND METHODS

HbA1c values were measured by high-performance liquid chromatography (HPLC) in 12 nondiabetic subjects (7 men and 5 women; median age, 40 years [range, 21–55 years]) on 10 fortnightly occasions. The nondiabetic index of individuality (IOI) for HbA1c (i.e., the square root of the ratio of intra- to interindividual variance) was determined. Any test with an IOI of 1.4 has the most potential in disease screening, while one of 0.6 will be of little value.

RESULTS

The analytical variance contributed to 9% of the total test variance, intraindividual variance, 6%; and interindividual variance, 85%. The IOI was, therefore, only 0.27. Thus, nondiabetic HbA1c values vary markedly between subjects, while values in the same individual change little with time. As such, to lie outside the assay reference range, the HbA1c values of some nondiabetic subjects must exceed 12 SD from their usual mean value, while in others a change of only 2 SD would be sufficient.

CONCLUSIONS

This fundamental characteristic of HbA1c means that even if analytical methods improve, glycated hemoglobin measurements will always be of limited value when screening for type 2 diabetes. If similar interindividual differences also exist in diabetic subjects, then patients with the same glycemic control may vary by at least 1–2%, which has implications in setting glycated hemoglobin targets.
Angiotensinogen T235 and ACE Insertion/Deletion Polymorphisms Associated With Albuminuria in Chinese Type 2 Diabetic Patients
Authors: Young Robert P , Chan Juliana C N , Critchley Julian A J H , Poon Emily , Nicholls Gary , Cockram Clive S
Published: March 2007

OBJECTIVE

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the frequencies of these genotypes have also been reported. To date, most of these studies have been performed in white and Japanese populations. In this study, we examined the associations between albuminuria and RAS genetic polymorphisms in Chinese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In a case-control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT) gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin excretion (UAE) was defined as ≥ 30 mg/day on at least two occasions during a 6-week study period.

RESULTS

Compared with whites, there were high frequencies of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2 diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and 3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively. Although 9% of subjects carried the C allele, the AT1 CC genotype was not found in either group. Chinese type 2 diabetic patients with increased albuminuria (n = 56) had higher systolic blood pressure (160 ± 26 mmHg vs 145 ± 27 mmHg, P < 0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3–6.8]) and the T allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3–5.4]) were associated with an increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8 mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in patients with normotension (56 mg/day [n = 19] for patients with the TT genotype vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 ± 29 U/l vs. 60.5 ± 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4 mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype or D allele and hypertension.

CONCLUSIONS

The high frequencies of the TT genotype and T allele in Chinese populations may contribute to the high prevalence of albuminuria in patients with type 2 diabetes. The possibility of synergism between the AGT TT genotype and the ACE D allele should also be explored.
Glomerular Charge and Size Selectivity Assessed by Changes in Salt Intake in Type 2 Diabetic Patients
Authors: Yoshioka Katsunobu , Imanishi Masahito , Konishi Yoshio , Sato Toshihiko , Tanaka Shiro , Kimura Genjiro , Fujii Satoru
Published: March 2007

OBJECTIVE

To evaluate glomerular charge selectivity in patients with type 2 diabetes, we studied changes in fractional clearance of proteins with different sizes and charges when patients were placed on two diets with different salt contents.

RESEARCH DESIGN AND METHODS

Nineteen patients with type 2 diabetes and normoalbuminuria (<20 μg/min, n = 8), microalbuminuria (20–100 μg/min, n = 7), or advanced albuminuria (>100 ug/min, n = 4) were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255 mEq of sodium daily) for 1 week, and then on the other diet, in random order. Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on the last 3 days of each diet.

RESULTS

In patients with normoalbuminuria, the high-salt diet increased the fractional clearance of IgG, which is electrically neutral, but the fractional clearance of albumin, which is anionic, was unaltered, suggesting that the pore charge of the glomerular barrier was unaffected. However, in patients with microalbuminuria, the high-salt diet increased the fractional clearances of IgG and albumin equally, indicating some neutralization of the pore charge. Fractional clearance of IgG in these first two groups was similar when salt intake was low, so pore size was the same in these groups. In patients with advanced albuminuria, fractional clearance of IgG was higher than in the other groups, indicating that size selectivity had worsened.

CONCLUSIONS

In type 2 diabetic patients, charge selectivity is lost before size selectivity as diabetic nephropathy progresses.
Serum Leptin Levels in Smokers With Type 2 Diabetes
Authors: Yoshinari Mototaka , Wakisaka Masanori , Fujishima Masatoshi
Published: March 2007

OBJECTIVE

To elucidate the molecular mechanism of smoking cessation and its relationship to body weight gain, the effects of smoking on the serum levels of leptin were studied in Japanese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

The serum levels of leptin after an overnight fast in 37 adult male Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were assayed using radioimmunoassay In addition, the serum leptin levels in four nondiabetic smokers were measured before and 2 weeks after quitting smoking.

RESULTS

Smokers and nonsmokers did not differ in age, BM1, or levels of blood glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 ± 0.18 vs. 1.32 ± 0.24 mmol/1 for smokers and nonsmokers, respectively, P = 0.002). The mean serum leptin level of smokers did not differ from that of nonsmokers (3.8 ± 1.9 vs. 3.8 ± 1.6 ng/ml). The leptin level correlated with the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001, respectively). The leptin levels in four heavy smokers showed no change after the subjects quit smoking (3.3 ± 1.0 vs. 3.8 ± 1.8 ng/ml, before and after quitting, respectively).

CONCLUSIONS

Because smoking did not affect the leptin levels, the effects of quitting smoking on the fuel metabolism appear to be due to some other factors.
Prevalence of Diabetes, Impaired Fasting Glucose, and Impaired Glucose Tolerance in U.S. Adults: The Third National Health and Nutrition Examination Survey, 1988–1994
Authors: Harris Maureen I , Flegal Katherine M , Cowie Catherine C , Eberhardt Mark S , Goldstein David E , Little Randie R , Wiedmeyer Hsiao-Mei , Byrd-Holt Danita D
Published: March 2007

OBJECTIVE

To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES 111) and prior Health and Nutrition Examination Surveys (HANESs).

RESEARCH DESIGN AND METHODS

NHANES III contained a probability sample of 18,825 U.S. adults ≥20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976–1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980–1985 World Health Organization (WHO) oral glucose tolerance test criteria.

RESULTS

Prevalence of diagnosed diabetes in 1988–1994 was estimated to be 5.1% for U.S. adults ≥20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose ≥126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to <126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40–74 years of age increased from 8.9% in the period 1976–1980 to 12.3% by 1988–1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%).

CONCLUSIONS

The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S
Incidence and Determinants of Microalbuminuria in Koreans With Type 2 Diabetes
Authors: Park Joong-Yeol , Kim Hong-Kyu , Chung Yun E , Kim Sang W , Hong Sung K , Lee Ki-Up
Published: March 2007

OBJECTIVE

The incidence of diabetic nephropathy in type 2 diabetes differs widely by race. Although clinical proteinuria is reportedly more common in East Asian type 2 diabetic patients than in their Caucasian counterparts, data on the incidence of microalbuminuria are not available. This study was undertaken to investigate the incidence and the determinants of microalbuminuria in Korean type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

A cohort of 188 Korean type 2 diabetic patients with initial normoalbuminuria were followed prospectively for 5.5 ± 0.9 years in an outpatient clinic of a university hospital. The incidence of elevated urinary albumin excretion (UAE) (>20 μg/min) and its relationship with baseline characteristics and follow-up data were determined.

RESULTS

Of the 146 patients who finished the study, 37 showed persistently elevated UAE during follow-up, giving an incidence of 52/1,000 person-years. Age, duration of diabetes, and baseline UAE were significantly higher in the progressors than in the nonprogressors. More patients in the progressor group had retinopathy at baseline and at the end of follow-up. The mean values of fasting plasma glucose, HbA1, and systolic and diastolic blood pressure during the follow-up period were significantly higher in the progressors than in the nonprogressors. Cox proportional hazards analysis revealed that presence of retinopathy, duration of diabetes, mean fasting plasma glucose, and mean systolic blood pressure during follow-up are independent variables that have a statistically significant influence on the development of microalbuminuria.

CONCLUSIONS

The incidence of microalbuminuria in Korean type 2 diabetic patients is lower than that reported in Pima Indians with type 2 diabetes but is as high as that in Caucasians with type 1 diabetes. Presence of diabetic retinopathy, poor glycemic control, and high blood pressure are risk factors for development of microalbuminuria in Koreans with type 2 diabetes.
The Effect of Glycemic Control in the Pre-Conception Period and Early Pregnancy on Birth Weight in Women With IDDM
Authors: Gold Ann E , Reilly Rena , Little Jill , Walker James D
Published: March 2007

OBJECTIVE

To examine data from pregnancies in women with IDDM to assess the relative effects of mean glycosylated hemoglobin levels before conception, at booking, and during the 3 trimesters of pregnancy on birth weight. Good glycemic control during pregnancy in women with IDDM is important to minimize the risk of fetal malformation and macrosomia. Recent studies have suggested that glycemic control in the 1st trimester is more important than glycemic control during the 2nd or 3rd trimesters.

RESEARCH DESIGN AND METHODS

The case records of 65 deliveries to women with IDDM were reviewed. Fifty-seven deliveries were included in the present study. Of the deliveries reviewed, 32 women were in their first pregnancy and 25 women were multiparous. Only viable pregnancies were included because the major outcome variable of interest was birth weight. Glycosylated hemoglobin was recorded for each time period.

RESULTS

The median standardized birth weight was 1.1 SD higher than the nondiabetic mean. When pregnancies, in which the birth weight was greater than 1 SD above the nondiabetic mean, were compared with pregnancies, in which birth weight was less than 1 SD above the mean, significant differences were observed between the groups in HbA1 at 6–12 months pre-conception (10.0 ± 2.3 vs. 8.6 ± 1.4%, P = 0.02), at 0–6 months pre-conception (10.2 ± 2.4 vs. 8.7 ± 2.0%, P = 0.03), at booking (9.5 ± 2.2 vs. 8.4 ± 1.6%, P = 0.04), and at 0–12 weeks' gestation (9.5 ± 2.2 vs. 8.0 ± 1.3%, P = 0.04), but HbA1 later in pregnancy did not differ significantly between the groups. Correlational analysis of all 57 pregnancies revealed significant correlations between birth weight and HbA1 at 0–6 months pre-conception (r = 0.44, P = 0.002), at booking (r = 0.43, P = 0.001), at 0–12 weeks' gestation (r = 0.48, P = 0.001), at 12–24 weeks' gestation (r = 0.45, P = 0.001), and at 24 weeks to term (r = 0.34, P = 0.009). However, with stepwise regression analysis, only HbA1 at 0–12 weeks' gestation entered into the equation with a multiple r value of 0.48.

CONCLUSIONS

Glycemic control in the immediate pre-conception period and early 1st trimester appears to have a greater influence on birth weight than does glycemic control during the later weeks of pregnancy.
The Prevalence of Diabetes in a Swedish Population of 280,411 Inhabitants: A report from the Skaraborg Diabetes Registry
Authors: Berger Bo , Stenström Gunnar , Chang Yue-Fang , Sundkvist Göran
Published: March 2007

OBJECTIVE

To estimate the prevalence of known diabetes in a Swedish county (Skaraborg) and to evaluate capture-recapture methods for validation of the diabetes prevalence.

RESEARCH DESIGN AND METHODS

Four sources were used to find known diabetic patients: 1) the Skaraborg Diabetes Registry (SDR), a case-finding inventory 2) an administrative hospital registry 3) a registry for the retinopathy screening program, and 4) a pharmacy prescription inventory. The capture-recapture method was applied to various combinations of sources to determine the prevalence of diabetes.

RESULTS

The completeness of the SDR was 88.4 ± 1.3%, indicating a diabetes prevalence of 3.20 ± 0.08%. When the SDR was not used as one of the sources, the estimated prevalence varied between 2.2 and 4.5%.

CONCLUSIONS

A case-finding registry is important in reliably estimating the prevalence of diabetes.
Physical Activity and NIDDM in African-Americans: The Pitt County Study
Authors: James Sherman A , Jamjoum Lama , Raghunathan T E , Strogatz David S , Furth Eugene D , Khazanie Prabhaker G
Published: March 2007

OBJECTIVE

Studies directly examining the association between physical activity and NIDDM in African-Americans are rare. Consequently, the strength of this association in this ethnic minority group remains unclear. The current study broadly characterizes the types of physical activity engaged in by a community sample of working-class African-Americans and then quantifies the association between physical activity and NIDDM risk in this population.

RESEARCH DESIGN AND METHODS

During the 1993 reexamination of participants in the Pitt County Study in North Carolina, data on NIDDM history, current use of insulin or oral hypoglycemic drugs, and ∼12-h overnight fasting blood glucose (FBG) were obtained from 598 women and 318 men, ages 30-55 years. The presence of NIDDM was determined by current insulin or medication use and FBG ≥ 140 mg/dl. Study participants were assigned to one of four categories of physical activity: strenuous, moderate, low, or inactive.

RESULTS

The weighted prevalence of NIDDM in the sample was 7.1%. After adjustment was made for age, sex, education, BMI, and waist-to-hip ratio, NIDDM risk for moderately active subjects was one-third that for the physically inactive subjects (odds ratio [OR], 0.35; 95% CI, 0.12-0.98). The ORs for low (OR, 0.51; 95% CI, 0.20-1.29) and strenuous (OR, 0.65; 95% CI, 0.26-1.63) activity also tended to be lower. A summary OR that contrasted any activity versus no activity was 0.51 (95% CI, 0.23-1.13).

CONCLUSIONS

Moderate physical activity was strongly associated with reduced risk for NIDDM in this sample. While replication of these findings is needed, public health interventions designed to increase moderate (leisure-time) physical activity in black adults should be strongly encouraged.
Development of Proliferative Diabetic Retinopathy in African-Americans and Whites With Type 1 Diabetes
Authors: Arfken Cynthia L , Reno Philip L , Santiago Julio V , Klein Ronald
Published: March 2007

OBJECTIVE

To investigate the comparable risk of developing proliferative diabetic retinopathy (PDR) in African-Americans and whites with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Using a cohort design with the sample drawn from medical records, the sample consisted of 312 people with type 1 diabetes (97 African-Americans, 215 whites) having at least two visits to a Model Demonstration Unit with gradeable fundus photographs (stereo, color, 7 standard fields). Excluded were subjects with preexisting or treated PDR or hemoglobinopathy. Masked grading of the fundus photographs was conducted at the Wisconsin Reading Center.

RESULTS

At baseline, African-Americans had poorer glycemic control (mean HbA1 of 11.3 vs. 10.0%, P < 0.0001), higher systolic blood pressure (mean of 117 vs. 110 mmHg, P < 0.001), and were older (mean of 26.8 vs. 19.3 years, P < 0.0001) than the white subjects. African-Americans also tended to have slightly longer duration of diabetes and length of follow- up. In the African-Americans, 17.5% developed PDR, compared with 10.2% in the 215 whites, for an odds ratio (OR) of 1.86 (95% CI 0.93–3.70). When adjusted for baseline glycemic control, retinopathy grade, and length of follow-up, race was not a significant risk factor (OR = 0.73, 95% CI 0.30–1.78).

CONCLUSIONS

African-Americans with type 1 diabetes may have a higher rate of developing PDR. The observed racial difference, however, is attributable to the presence of a worse risk factor profile, especially to poorer glycemic control. Efforts should be expanded to improve the care for all individuals with poor glycemic control.