Effects of Changing the Amount and Source of Dietary Carbohydrates on Symptoms and Dietary Satisfaction Over a 1-Year Period in Subjects with Type 2 Diabetes: Canadian Trial of Carbohydrates in Diabetes (CCD).

OBJECTIVES: To determine the long-term effects of changing the amount or source of dietary carbohydrate on quality of life (QOL), symptoms and dietary satisfaction in people with type 2 diabetes. METHODS: Subjects with diabetes treated by diet alone (n=162) were randomly assigned to high-carbohydrate/high-glycemic-index (HGI) diets; high-carbohydrate/low-glycemic-index (LGI) diets; or lower-carbohydrate/high-monounsaturated-fat (LC) diets for 1 year. We measured QOL at baseline and at study's end, and we measured symptoms and dietary satisfaction quarterly. RESULTS: The HGI, LGI and LC diets contained, respectively, 47±1, 52±1 and 40±1% energy carbohydrate; 30±1, 27±1 and 40±1% fat with GI 64±0.4, 55±0.4 and 59±0.4. Significantly more participants reported increased flatulence on LGI than on LC and HGI diets at 3 months (41%, 19%, 14%; p<0.05), but not at 12 months (29%, 17%, 17%; ns). Abdominal distension was more severe (46% vs. 14%, 19%; p<0.05), and headache less severe (8% vs. 22%, 23%; p<0.05) on LGI than on both other diets. Increased appetite was more severe on LC (33%) than on HGI diets (14%, p<0.05). Joint/limb pains were less severe on LGI (16%) than HGI (28%) diets. LC elicited more severe gloomy thoughts (23%) than LGI (4%; p<0.05) but greater dietary-satisfaction (70%; p<0.05) than LGI (40%) and HGI (48%) diets. For all diets, glycated hemoglobin (A1C) levels increased less in those who gained less weight, had less increased appetite and were more satisfied with the enjoyment obtained from eating. CONCLUSIONS: Each diet elicited increased severity of 1 or more symptoms than the other diets. Although overall dietary satisfaction was greater on the 40% carbohydrate diet than on the 50% carbohydrate diet, the LGI diet was no less satisfying than the HGI diet. Changes in appetite and dietary satisfaction may influence body weight and glycemic control, or vice-versa.

Effectiveness of the First step Program delivered by professionals versus peers.

BACKGROUND: To compare the effectiveness of a theory-based lifestyle physical activity (PA) program delivered to individuals with type 2 diabetes in diabetes education centers by professionals and peers. METHODS: Changes over 16 weeks in PA (steps/day) and related variables (weight, waist girth, resting heart rate, systolic and diastolic blood pressures) were compared (RMANOVA) for two groups: 157 participants led by 13 different professionals versus 63 participants led by 5 peer leaders. RESULTS: Overall, the 81 male and 139 female participants (age = 55.7 +/- 7.3 years, BMI = 35.2 +/- 6.6) showed an incremental change of 4,059 +/- 3,563 steps/day, which translates into an extra 37 minutes of daily walking (P < .001). Statistically significant improvements were also seen in weight, waist girth, and blood pressure (all P < .001) and resting heart rate (P < .05). There were no significant differences in outcomes between professional and peer-led groups. CONCLUSIONS: A theory-based behavior modification program featuring simple feedback and monitoring tools, and with a proven element of flexibility in delivery, can be effective under real-world conditions while addressing inevitable concerns about resource allocation. Program delivery by peer leaders, in particular, could address a potential obstacle to dissemination by helping to alleviate existing high caseload demands on diabetes educators.

Evaluation of a self-awareness intervention for adults with type 1 diabetes and hypoglycemia unawareness.

The purpose of this prospective before-and-after study was to determine whether there are psychosocial and physical benefits of a self-awareness intervention for adults with type 1 diabetes and hypoglycemia unawareness (HU). A total of 29 adults participated in the self-awareness intervention of 8 sessions, each lasting 3 hours. Psychosocial (integration, diabetes quality of life) and physical (number of body cues, HU-related events, HbA1c) measures were taken at baseline and at 6, 12, and 18 months post-intervention. Post-intervention the participants detected more cues of euglycemia and hypoglycemia and experienced significant increases in integration and metabolic control (HbA1c). The number of HU-related events was not decreased and diabetes quality-of-life results were unstable. A self-awareness intervention can have physical and psychosocial benefits and has implications for diabetes education. This intervention needs to be tested in a multi-centre randomized control trial.

The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein.

BACKGROUND: The optimal source and amount of dietary carbohydrate for managing type 2 diabetes (T2DM) are unknown. OBJECTIVE: We aimed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin (HbA1c), plasma glucose, lipids, and C-reactive protein (CRP) in T2DM patients. DESIGN: Subjects with T2DM managed by diet alone (n=162) were randomly assigned to receive high-carbohydrate, high-glycemic-index (high-GI), high-carbohydrate, low-glycemic-index (low-GI), or low-carbohydrate, high-monounsaturated-fat (low-CHO) diets for 1 y. RESULTS: The high-GI, low-GI, and low-CHO diets contained, respectively, 47%, 52%, and 39% of energy as carbohydrate and 31%, 27%, and 40% of energy as fat; they had GIs of 63, 55, and 59, respectively. Body weight and HbA1c did not differ significantly between diets. Fasting glucose was higher (P=0.041), but 2-h postload glucose was lower (P=0.010) after 12 mo of the low-GI diet. With the low-GI diet, overall mean triacylglycerol was 12% higher and HDL cholesterol 4% lower than with the low-CHO diet (P<0.05), but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo (time x diet interaction, P=0.044). Overall mean CRP with the low-GI diet, 1.95 mg/L, was 30% less than that with the high-GI diet, 2.75 mg/L (P=0.0078); the concentration with the low-CHO diet, 2.35 mg/L, was intermediate. CONCLUSIONS: In subjects with T2DM managed by diet alone with optimal glycemic control, long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate. Differences in total:HDL cholesterol among diets had disappeared by 6 mo. However, because of sustained reductions in postprandial glucose and CRP, a low-GI diet may be preferred for the dietary management of T2DM.

Genetic polymorphisms of tumor necrosis factor-alpha modify the association between dietary polyunsaturated fatty acids and fasting HDL-cholesterol and apo A-I concentrations.

BACKGROUND: Heterogeneity in circulating lipid concentrations in response to dietary polyunsaturated fatty acids (PUFAs) may be due, in part, to genetic variations. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that can induce hyperlipidemia and is known to be modulated by dietary PUFAs. OBJECTIVE: The objective was to determine whether TNF-alpha genotypes modify the association between dietary PUFA intake and serum lipid concentrations. DESIGN: The study involved 53 men and 56 women aged 42-75 y with type 2 diabetes. Dietary intakes were assessed with the use of a 3-d food record, and blood samples were collected to determine fasting serum lipids. DNA was isolated from blood for genotyping by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G-->A and -308G-->A polymorphisms. RESULTS: PUFA intake was positively associated with serum HDL cholesterol in carriers of the -238A allele (beta = 0.06 +/- 0.03 mmol/L per 1% of energy from PUFAs; P = 0.03), but negatively associated in those with the -238GG genotype (beta = -0.03 +/- 0.01, P = 0.03) (P = 0.004 for interaction). PUFA intake was inversely associated with HDL cholesterol in carriers of the -308A allele (beta = -0.07 +/- 0.02, P = 0.002), but not in those with the -308GG genotype (beta = 0.02 +/- 0.02, P = 0.13) (P = 0.001 for interaction). A stronger gene x diet interaction was observed when the polymorphisms at the 2 positions (-238/-308) were combined (P = 0.0003). Similar effects were observed for apolipoprotein A-I, but not with other dietary fatty acids and serum lipids. CONCLUSION: TNF-alpha genotypes modify the relation between dietary PUFA intake and HDL-cholesterol concentrations. These findings suggest that genetic variations affecting inflammation may explain some of the inconsistencies between previous studies relating PUFA intake and circulating HDL.

Tumor necrosis factor alpha -238G>A genotype alters postprandial plasma levels of free fatty acids in obese individuals with type 2 diabetes mellitus.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that impairs insulin action and alters lipid metabolism. We investigated the effects of genetic polymorphisms of TNF-alpha on circulating biomarkers of insulin resistance and lipid metabolism during an 8-hour metabolic profile test and a 2-hour oral glucose tolerance test in subjects with type 2 diabetes mellitus. Subjects (N = 123) recruited were type 2 diabetic men (n = 56) and women (n = 67) aged 36 to 75 years with a body mass index of at least 25 kg/m(2). Blood samples were collected to determine postprandial changes in circulating lipid levels and biomarkers of insulin resistance. Subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G>A, -308G>A, and -863C>A polymorphisms. Compared with subjects who were homozygous for the -238G allele, carriers of the -238A allele had an altered ability to suppress postprandial free fatty acids as shown by an increased net incremental area under the curve (0.26 +/- 2.44 vs -1.33 +/- 2.71 mEq h(-1) L(-1), P = .002) during the 8-hour metabolic profile test. This effect was observed in obese (1.04 +/- 2.42 vs -1.68 +/- 2.70 mEq h(-1) L(-1), P = .0004) but not in non-obese (-0.63 +/- 2.20 vs -0.95 +/- 2.71 mEq h(-1) L(-1), P = .6) individuals. Among obese subjects, carriers of the -308A allele had greater insulin resistance as estimated by the homeostasis model assessment of insulin resistance index (4.36 +/- 2.83 vs 2.85 +/- 1.75, P = .01), but no differences were observed among non-obese subjects (2.19 +/- 1.24 vs 1.97 +/- 0.90, P = .6). Our findings suggest that the -238G>A and -308G>A polymorphisms of TNF-alpha alter circulating free fatty acids and insulin resistance in obese subjects with type 2 diabetes mellitus.

Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy.

The etiology of acquired partial lipodystrophy (APL, also called "Barraquer-Simons syndrome") is unknown. Genomic DNA mutations affecting the nuclear lamina protein lamin A cause inherited partial lipodystrophy but are not found in patients with APL. Because it also encodes a nuclear lamina protein (lamin B2) and its genomic structure was recently reannotated, we sequenced LMNB2 as a candidate gene in nine white patients with APL. In four patients, we found three new rare mutations in LMNB2: intron 1 -6G-->T, exon 5 c.643G-->A (p.R215Q; in two patients), and exon 8 c.1218G-->A (p.A407T). The combined frequency of these mutations was 0.222 in the patients with APL, compared with 0.0018 in a multiethnic control sample of 1,100 subjects (P = 2.1 x 10-7) and 0.0045 in a sample of 330 white controls (P = 1.2 x 10-5). These novel heterozygous mutations are the first reported for LMNB2, are the first reported among patients with APL, and indicate how sequencing of a reannotated candidate gene can reveal new disease-associated mutations.

Six-month evaluation of a diabetes self-awareness intervention.

The purpose of this pilot study was to evaluate the effectiveness of a self-awareness intervention in promoting increased awareness of body cues associated with various levels of glycemia and in enhancing well-being in persons with Type I diabetes and hypoglycemia unawareness. Study results indicated that participants could identify more cues of normal blood glucose; experienced fewer blood glucose levels below 3.5 mmol/L, fewer hypoglycemia unawareness-related events, and improved glycemia; but reported lower diabetes quality of life. The self-awareness intervention represents an innovative theory-based approach for helping clients with Type I diabetes and hypoglycemia unawareness to achieve positive health outcomes.

Metastatic secondary fibrosarcoma of bone responsive to repeated courses of Ifosfamide and associated with hypoglycemia.

We present a case of a 40-year-old man with secondary fibrosarcoma of bone, arising from a non-ossifying fibroma. He subsequently developed metastatic disease that responded to four successive chemotherapy courses, the last three using the same dose/schedule of single agent ifosfamide. Eventual rapid progression of a huge intra-abdominal mass was associated with the syndrome of extrapancreatic tumour hypoglycemia (EPTH). The clinicopathological behaviour of fibrosarcoma of bone, and the mechanism of EPTH are discussed.

Pedometer-determined ambulatory activity in individuals with type 2 diabetes.

This cross-sectional study presents the first normative data on pedometer-determined ambulatory activity, defined as steps/day, in 160 (98 males, 62 females; age=52.4 +/- 5.3 years; BMI=32.3 +/- 5.7) free-living individuals with type 2 diabetes. Participants took 6662 +/- 3077 steps per day, less than that reported in nondiabetic samples and more than that reported for samples living with more restrictive chronic conditions including claudication, joint replacement, chronic obstructive lung disease, and chronic heart failure. Steps/day and BMI were inversely and significantly correlated (r=-0.27, P<0.01). Further, there was a significant difference between BMI categories (from normal weight to obesity class III) with regard to steps/day (F=2.96, P<0.05). The difference was most apparent between the highest obesity classes (II and III) and normal weight categories. This data is useful for sample comparison purposes. In addition the standard deviation or variance estimates can be used to calculate samples sizes for intervention efforts. Objective quantification of ambulatory activity via simple and inexpensive pedometers permits researchers and practitioners to easily screen for level of activity along a continuum. This study opens the door for future research and clinical applications including identifying threshold values related to important health outcomes and evaluating incremental change due to various interventions in this population.

Colocalization of pancreatic polypeptide and insulin in secretory granules of a pancreatic endocrine neoplasm.

A 45-year-old woman presented with clinical symptoms of hypoglycemia of 4 months duration. Laboratory testing confirmed hyperinsulinemia; mild hypercalcemia and hypergastrine-mia were also documented. At the time of operation, 3 pancreatic endocrine neoplasms were found, and a diagnosis of multiple endocrine neoplasia type I was made. Immunohistochem-istry and immunoelectron microscopy showed all the tumors to be plurihormonal, each containing three or more of the following: insulin, glucagon, somatostatin, pancreatic polypep-tide, gastrin, and serotonin. Electron microscopy of 2 tumors revealed numerous atypical granules. In 1 tumor, pancreatic polypeptide and insulin were colocalized in secretory granules by dual-staining immunoelectron microscopy. To our knowledge, this combination of hormones has not been described previously in pancreatic endocrine neoplasms and suggests that such neoplasms, like mature pancreatic endocrine cells, may originate from pluripotential common precursor cells.