Increased passive ankle stiffness and reduced dorsiflexion range of motion in individuals with diabetes mellitus

BACKGROUND: The purpose of our study was to compare ankle range of motion and stiffness in individuals with and without diabetes mellitus using a reliable and valid technique and to document the effect of knee flexion and severity of pathology on ankle range of motion and stiffness. METHODS: Twenty-five individuals with diabetes mellitus and 64 nondiabetic individuals, similar in age and gender profile, participated in this study. RESULTS: Results revealed that individuals with diabetes mellitus had both significantly lower peak dorsiflexion range of motion (5.1 and 11.5 degrees, p < 0.001) and higher passive ankle stiffness (0.016 and 0.008 Nm/kg/degree, p < 0.01) than non-diabetic individuals. In individuals with diabetes mellitus, a positive relationship between glycemic control and duration of diabetes mellitus and ankle stiffness ((r(2) = 0.48 and 0.24 respectively, p < 0.01 for both) was found. CONCLUSION: While decreased range of motion and increased stiffness in the diabetes mellitus population seem clinically intuitive, as far as we know this is the first study to confirm the concurrent existence of both these findings in the plantarflexors in individuals with diabetes mellitus. We applied a reliable and valid technique, one that allowed control of confounding factors such as knee flexion position and differences in determination of end range of motion, and documented a mean 41% loss in dorsiflexion excursion. Changes in the muscle, stemming from underlying pathology, are hypothesized to account for a significant part of the lost range of motion. Changes in ankle range of motion and stiffness may have important implications in plantar loading and ulcer formation.     

Large glomerular size in Pima Indians: lack of change with diabetic nephropathy.

The mean glomerular volume, glomerular fraction of cortical volume, and percentage of obsolescent glomeruli were calculated in kidney specimens from autopsies on 34 Pima Indians, of whom 15 had non-insulin dependent diabetes mellitus and kidney disease of diabetes mellitus. These values were compared with those of black, white, and non-Pima native American individuals without diabetes mellitus. Glomerular volume in the Pima Indians was similar in the diabetic and nondiabetic subjects and significantly greater than in the white subjects. Black and non-Pima native American individuals had glomerular volumes intermediate between white individuals and Pima Indians. The mean glomerular volume was not affected by the number of obsolescent glomeruli in diabetic Pima Indians. The glomerular volume fraction was greater in the Pimas than in the other groups. These data showed that glomerular volume in the Pima Indians was significantly greater than that in white subjects. There was no difference between diabetic and nondiabetics Pimas, and glomerular size was not correlated with the presence or degree of glomerulosclerosis in this population.     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.     

Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from “common soil”. The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.     

HL-A system and diabetes mellitus.

HL-A antigens were determined in 100 patients with diabetes mellitus. When the data are combined with that from other studies, there is a definite positive association of acute-onset juvenile diabetes mellitus with HL-A8 and W15. Four families are described in which two or more members with this type of diabetes are present, and in each family, affected individuals share a haplotype including HL-A8 or W15. These findings are consistent with the possible role of immune response genes in the HL-A chromosomal region which might control the immune response to virus infections capable of producing islet cell damage.     

Does type 2 diabetes mellitus delay renal failure in autosomal dominant polycystic kidney disease?

Autosomal dominant polycystic kidney disease (ADPKD) is a common renal disease without an effective therapeutic intervention to delay renal failure. Within kindreds, renal dysfunction often develops at a similar age in affected individuals, although there are known modifying factors. Two kindreds with ADPKD have shown a striking pattern of delayed onset of renal insufficiency in those individuals also suffering from type 2 diabetes mellitus. Eight nondiabetic patients with ADPKD had onset of dialysis or renal death at ages 38-52 years, (mean +/- SEM 46 +/- 1.9, n = 7) as compared with four diabetics who started dialysis or are still off dialysis at the age of 61 +/- 2.8 years (p < 0.01). Two of the four diabetics still have reasonable renal function at age 61 and 66. The diabetes was diagnosed at age 32 +/- 2 years and was treated with oral hypoglycemics for 19 +/- 2 years before institution of insulin. Cardiovascular disease dominated the clinical picture in the diabetics. In conclusion, onset of renal failure in ADPKD was delayed for over 15 years in individuals who also suffered from type 2 diabetes mellitus, in two ADPKD kindreds. Possible mechanisms are discussed, including glibenclamide inhibition of the cystic fibrosis transmembrane conductance regulator. The striking delay associated with type 2 diabetes mellitus in ADPKD induced renal failure should be evaluated further.     

Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase

Elevated urinary albumin excretion in patients with type 1 diabetes reverts to normoalbuminuria in a majority of patients but advances toward proteinuria in some. In order to gain valuable insights into the early pathophysiology of diabetic nephropathy we evaluated the association of kidney tubular injury biomarkers with changes in albuminuria in patients with type 1 diabetes mellitus. Urine levels of kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and some inflammatory markers were determined in 38 healthy individuals and 659 patients with type 1 diabetes mellitus having varying degrees of albuminuria. Urinary interleukin-6, CXCL10/IP-10, NAG, and KIM-1 levels were very low in healthy individuals, increased in type 1 patients with normoalbuminuria, and were highest in diabetic patients that had microalbuminuria. Low baseline concentrations of urinary KIM-1 and NAG both individually and collectively were significantly associated with the regression of microalbuminuria over the subsequent 2 years; an effect independent of clinical characteristics. Progression and regression of microalbuminuria were unrelated to urinary levels of interleukins 6 and 8, CXCL10/IP-10, and monocyte chemoattractant protein-1. Thus our results show that lower urinary KIM-1 and NAG levels were associated with the regression of microalbuminuria in type 1 diabetes mellitus. Hence, tubular dysfunction is a critical component of the early course of diabetic nephropathy.     

Current and future impact of clinical gastrointestinal research on patient care in diabetes mellitus

The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus should provide additional options to improve their clinical outcomes.     

Similar risks of nephropathy in patients with type I or type II diabetes mellitus

It is commonly assumed that in patients the risks of developing nephropathy and uraemia are high in type I and low in type II diabetes mellitus. Since type II occurs mostly in elderly individuals with limited life expectancy and high cardiovascular mortality, the true risk may have been underestimated, as many patients do not survive to experience renal complications. To assess renal risk further, we evaluated all patients with type II and type I diabetes mellitus without severe secondary disease who were followed in the outpatient clinic between 1970 and 1985. The cumulative risk of proteinuria after 20 years of diabetes mellitus was 27% in type II and 28% in type I, the findings after 25 years were 57% and 46% respectively. The cumulative risk of renal failure, i.e. serum creatinine greater than 1.4 mg/dl, after 3 years of persisting proteinuria was 41% in both type II and type I, and after 5 years of proteinuria were 63% and 59% respectively. We conclude that the renal risk is similar in patients with type II and type I diabetes mellitus.     

Carbohydrate and lipid metabolism in chronic spinal cord injury

BACKGROUND: Abnormalities of carbohydrate and lipid metabolism are more common in the spinal cord injury (SCI) population than in the able-bodied population. This is an important consideration in the long-term care of individuals with SCI. DESIGN: Literature review. FINDINGS: When compared with the able-bodied population, people with SCI are more likely to have oral carbohydrate intolerance, insulin resistance, elevated low-density lipoprotein cholesterol, and reduced high-density lipoprotein cholesterol, associated with increased prevalences of diabetes mellitus and cardiovascular disease. CONCLUSIONS: Because of increased risk factors for diabetes mellitus and heart disease in individuals with SCI, modifiable risk factors should be addressed, eg, obesity, inactivity, dietary factors, and smoking. To reduce mortality and morbidity associated with these risk factors, periodic screening for carbohydrate and lipid abnormalities is recommended, with appropriate therapeutic interventions.     

Invited Review Carbohydrate And Lipid Metabolism In Chronic Spinal Cord Injury

Abstract

Background: Abnormalities of carbohydrate and lipid metabolism are more common in the spinal cord injury (SCI) population than in the able-bodied population. This is an important consideration in the long-term care of individuals with SCI.

Design: Literature review.

Findings: When compared with the able-bodied population, people with SCI are more likely to have oral carbohydrate intolerance, insulin resistance, elevated low-density lipoprotein cholesterol, and reduced high-density lipoprotein cholesterol, associated with increased prevalences of diabetes mellitus and cardiovascular disease.

Conclusions: Because of increased risk factors for diabetes mellitus and heart disease in individuals with SCI, modifiable risk factors should be addressed, eg, obesity, inactivity, dietary factors, and smoking. To reduce mortality and morbidity associated with these risk factors, periodic screening for carbohydrate and lipid abnormalities is recommended, with appropriate therapeutic interventions.     

Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions?

Clinicians should be cognizant of the close relationship that exists between two of the most common endocrine disorders, primary hypothyroidism and diabetes mellitus. This applies to patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM respectively). However, the association is greater in T1DM, probably because of the shared autoimmune predisposition. In patients with T2DM, the relationship is somewhat weaker and the explanation less clear-cut. Factors such as dietary iodine deficiency, metformin-induced thyroid stimulating hormone suppression and poor glycemic control may all be implicated. Further translational research is required for greater clarification. Biochemical screening for abnormal thyroid function in individuals who have diabetes is warranted, particularly in females with T1DM, and therapy with L-thyroxine appropriately instituted if hypothyroidism is confirmed.     

Myths about diabetes mellitus among non-diabetic individuals attending primary health care centers of karachi subrubs

Objective: To determine the myths and misconception about diabetes mellitus among non-diabetics attending primary health care centers of Gadap town, Karachi. Design: Cross-sectional study. Place and Duration of the Study: Primary Health Care Centers, Gadap Town, Karachi, during the month of July 2005. Patients and Methods: Data was collected from four primary health care centers, located at Gadap Town, Karachi, and about 198 non-diabetic patients, above 18 years of age, and resident of Gadap Town, coming consecutively during the month of July 2005, were interviewed after taking the informed consent by using a semi-structured pre-tested questionnaire regarding prevailing myths about diabetes mellitus. The data collected was entered and analyzed by using a statistical package SPSS 11.0. Myths are defined as stories shared by a group, as part of the cultural identity. Results:There were 198 participants in the study. Mean age of study participants was 40 years with standard deviation of 13, while approximately two thirds, 62.6%, were females. About 39% had history of type II diabetes mellitus in family. Overall myths related to diabetes mellitus were common among the individuals, males reported myths pre-dominantly contagiousness of diabetes (p= < 0.03), diabetics becoming more ill (p=<0.009) and belief in spiritual treatment for permanent cure of diabetes (p=< 0.006). People having 5-16 years of education were less misconceived as compared to illiterates. The variables that showed significant difference were over-eating, causing diabetes (p= < 0.006), diabetics falling ill more than others (p=< 0.04), eating less starch (p= < 0.0006) and alternative treatment like spiritual treatment (p=< 0.00001). Family history of diabetes was also found significantly associated with reporting myths. Conclusion: Frequency of reporting myths was significantly high in this study with preponderance of males, family history of diabetes mellitus and educational status. Education serves as protective factor, hence efforts should be made to promote education and health awareness regarding the disease, with more emphasis on addressing myths regarding diabetes mellitus.     

Antioxidant role of zinc in diabetes mellitus

Chronic hyperglycemia statue noticed in diabetes mellitus favors the manifestation of oxidative stress by increasing the production of reactive oxygen species and/or by reducing the antioxidant defense system activity.Zinc plays an important role in antioxidant defense in type2 diabetic patients by notably acting as a cofactor of the superoxide dismutase enzyme,by modulating the glutathione metabolism and metallothionein expression,by competing with iron and copper in the cell membrane and by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase enzyme.Zinc also improves the oxidative stress in these patients by reducing chronic hyperglycemia.It indeed promotes phosphorylation of insulin receptors by enhancing transport of glucose into cells.However,several studies reveal changes in zinc metabolism in individuals with type 2 diabetes mellitus and controversies remain regarding the effect of zinc supplementation in the improvement of oxidative stress in these patients.Faced with the serious challenge of the metabolic disorders related to oxidative stress in diabetes along with the importance of antioxidant nutrients in the control of this disease,new studies may contribute to improve our understanding of the role played by zinc against oxidative stress and its connection with type 2 diabetes mellitus prognosis.This could serve as a prelude to the development of prevention strategies and treatment of disorders associated with this chronic disease.     

Disc degeneration and bone density in monozygotic twins discordant for insulin-dependent diabetes mellitus.

The effects of insulin-dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin-dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dual-energy x-ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1-0.3% lower (p = 0.87-0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate disc degeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin-dependent diabetes mellitus has any major effect on bone density or disc degeneration.     

The growing volume of diabetes-related dialysis: a population based study.

BACKGROUND: End-stage renal failure requiring dialysis is one of the most serious complications of diabetes mellitus, and diabetes is the most common cause of end-stage renal failure. The aim of this large, observational study is to describe the population-based incidence and prevalence rates and outcomes of diabetic individuals in Ontario, Canada who require dialysis therapy. METHODS: Two cohorts of patients, those with diabetes and those without, were created between April 1, 1994 and March 31, 2000 (total of approximately 8.4 million) and followed until March 31, 2001 using several large, linked administrative databases at the Institute for Clinical Evaluative Sciences. The incidence, prevalence and mortality on dialysis for each cohort were determined. A multivariate Cox proportional hazards analysis, adjusting for age, sex and co-morbidity, was used to determine the independent impact of diabetes on patient survival. RESULTS: The average annual incidence rate of dialysis was 12 times greater in persons with diabetes (130 per 100,000) vs without diabetes (11 per 100,000). By 1999-2000, diabetic patients comprised 51% of the incident dialysis population. The average annual prevalence rate was 10 times greater in the diabetic cohort. Patients with diabetes had more co-morbidities at the start of dialysis and poorer 3 year survival (55 vs 68%; P < 0.0001). CONCLUSIONS: The incident and prevalent rates of dialysis for patients with diabetes mellitus are many times the rates of those without diabetes. Patients with diabetes mellitus often start dialysis with significant co-morbidities, which may contribute to the relatively high rate of mortality on dialysis.     

Sodium-glucose cotransporter 2 inhibitors (SGLT2i): renal implications

International Urology and Nephrology - Type 2 diabetes mellitus (DM2) is a chronic condition that affects more than 400 million individuals worldwide. In DM2 patients, an appropriate glycemic...     

Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta1 (PRKCB1) gene locus

Abnormal activation of protein kinase C-beta isoforms in the diabetic state has been implicated in the development of diabetic nephropathy. It is thus plausible that DNA sequence differences in the protein kinase C-beta1 gene (PRKCB1), which encodes both betaI and betaII isoforms, may influence susceptibility to nephropathy. Nine single-nucleotide polymorphisms (SNP) in PRKCB1 were tested for association with diabetic nephropathy in type I diabetes mellitus, by using both case-control and family-study designs. Allele and genotype distributions of two SNP in the promoter (--1504C/T and --546C/G) differed significantly between case patients and control patients (P < 0.05). These associations were particularly strong with diabetes mellitus duration of <24 yr (P = 0.002). The risk of diabetic nephropathy was higher among carriers of the T allele of the --1504C/T SNP, compared with noncarriers (odds ratio, 2.54; 95% confidence interval, 1.39 to 4.62), and among carriers of the G allele of the --546C/G SNP (odds ratio, 2.45; 95% confidence interval, 1.37 to 4.38). Among individuals with diabetes mellitus duration of >/==" BORDER="0">24 yr, these two SNP were not associated with diabetic nephropathy. These positive findings were confirmed by using the family-based transmission disequilibrium test. The T-G haplotype, with both risk alleles, was transmitted more frequently than expected from heterozygous parents to offspring who developed diabetic nephropathy during the first 24 yr of diabetes mellitus. It is concluded that DNA sequence differences in the promoter of PRKCB1 contribute to diabetic nephropathy susceptibility in type I diabetes mellitus.