Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia.

AIMS/HYPOTHESES: We hypothesized that there is decreased synthesis of glutathione (GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular complications, and this is dependent on the degree of hyperglycemia. METHODS: In this case-control study, we recruited 16 patients with T2DM (7 without and 9 with microvascular complications), and 8 age- and sex-matched non-diabetic controls. We measured GSH synthesis rate using an infusion of [2H2]-glycine as isotopic tracer and collection of blood samples for liquid chromatography mass spectrometric analysis. RESULTS: Compared to the controls, T2DM patients had lower erythrocyte GSH concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes of changes in patients with complications were greater for both GSH concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to controls. There were no differences in GSH concentrations and synthesis rates between T2DM patients with and without complications (P-values > 0.1). Fasting glucose and HbA1c did not correlate with GSH concentration or synthesis rates (P-values > 0.17). CONCLUSIONS: Compared to non-diabetic controls, patients with T2DM have glutathione deficiency, especially if they have microvascular complications. This is probably due to reduced synthesis and increased irreversible utilization by non-glycemic mechanisms.

Population Reference Values and Prevalence Rates following Universal Screening for Subclinical Hypothyroidism during Pregnancy of an Afro-Caribbean Cohort.

BACKGROUND: Subclinical hypothyroidism (SCH) has been reported to be associated with adverse pregnancy outcomes, however universal screening and treatment is controversial. OBJECTIVES: Our objectives were to determine population-specific pregnancy reference values (R1) for serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) at 14 weeks' gestation, along with the prevalence of SCH and thyroid peroxidase antibody (TPOAb). METHODS: This was a prospective hospital-based cohort study. 1,402 subjects were recruited. Blood samples were obtained from 769 singleton pregnancies due to default between recruitment and scheduled blood draw. The prevalence of SCH was determined using R1, the laboratory non-pregnant reference values (R2) and previously recommended pregnancy reference values (R3). RESULTS: R1 for TSH and FT4 was 0.03-3.17 mU/l (mean ± SD, 1.1 ± 0.76) and 8.85-17.02 pmol/l (mean ± SD, 11.96 ± 2.06), respectively. The prevalence of SCH using reference values R1, R2 and R3 was 1.4% (11/769), 0.5% (4/769) and 1.9% (15/769). Prevalence was significantly greater using R3 when compared to R2 (p = 0.011). TPOAb prevalence was 2.6%. A significantly greater prevalence of TPOAb was found in subclinical hypothyroid subjects using all three reference values than in euthyroid subjects (∼25 vs. 2%, p < 0.05). CONCLUSIONS: These reference values are the first to be reported for an Afro-Caribbean population. Our findings support the use of pregnancy-specific reference values in our population.

Foot care and footwear practices among patients attending a specialist diabetes clinic in Jamaica.

This study aimed to estimate the proportion of patients at the University Hospital of the West Indies (UHWI) Diabetes Clinic who engage in recommended foot care and footwear practices. Seventy-two participants from the UHWI Diabetes Clinic completed an interviewer-administered questionnaire on foot care practices and types of footwear worn. Participants were a subset of a sex-stratified random sample of clinic attendees and were interviewed in 2010. Data analysis included frequency estimates of the various foot care practices and types of footwear worn. Participants had a mean age of 57.0±14.3 years and mean duration of diabetes of 17.0±10.3 years. Fifty-three percent of participants reported being taught how to care for their feet, while daily foot inspection was performed by approximately 60% of participants. Most participants (90%) reported daily use of moisturizing lotion on the feet but almost 50% used lotion between the toes. Approximately 85% of participants reported wearing shoes or slippers both indoors and outdoors but over 40% reported walking barefoot at some time. Thirteen percent wore special shoes for diabetes while over 80% wore shoes without socks at some time. Although much larger proportions reported wearing broad round toe shoes (82%) or leather shoes (64%), fairly high proportions reported wearing pointed toe shoes (39%), and 43% of women wore high heel shoes. In conclusion, approximately 60% of patients at the UHWI diabetic clinic engage in daily foot inspection and other recommended practices, but fairly high proportions reported foot care or footwear choices that should be avoided.

Early onset type 2 diabetes in Jamaica and in Mexico. Opportunities derived from an interethnic study.

Populations with Amerindian or African heritages are the one with the highest prevalence of diabetes worldwide. A large percentage of these individuals survived famine. However, the survival effect has become detrimental to their descendents living in an environment of caloric surplus. In countries, like Mexico and Jamaica, in which diabetes is highly prevalent, the onset of the disease happens at earlier ages. Our objective is to summarize diabetes data from Mexico and Jamaica and to discuss the opportunities that can result from an interethnic study. On one hand, the prevalence of diabetes in Jamaica is 17.9% in the 15+ age group. Jamaican researchers have built a cohort of families with early onset type 2 diabetes. In this population, this form of the disease is unrelated to MODY genes. On the other hand, the prevalence of diabetes in adult Mexicans is 14.4%. The group in which the greater percentual changes have occurred is the adults who are below the age of 40. More than two thirds of the early onset cases studied have a body mass index that is >25 kg/m2 and the clinical characteristics of metabolic syndrome. A minority of them has mutations in the MODY genes. The joint study of Mexican and Jamaican cohorts of early onset type 2 diabetes cases will be useful to identify new genetic and environmental players in the pathogenesis of this entity.

Multigenerational inheritance and clinical characteristics of three large pedigrees with early-onset type 2 diabetes in Jamaica.

OBJECTIVE: To document the existence and clinical characteristics of three large families with multigenerational inheritance of early-onset type 2 diabetes in Jamaica. METHODS: Three probands from large families with multigenerational inheritance of early-onset type 2 diabetes in at least three generations were detected at the University Hospital of the West Indies in Jamaica. Each proband at the time of diagnosis was < 25 years of age, was lean, and did not require insulin therapy. Clinical, metabolic, and genetic assessments were undertaken to profile the diabetes in the three families. RESULTS: Three pedigrees--BK, SU, and CA--consisting of 38, 48, and 113 members, respectively, with multigenerational inheritance of early-onset type 2 diabetes in at least three generations, were investigated. The mean age at diagnosis of the three pedigrees was 31.5 +/- 2.9 years, with 10 persons detected below 25 years of age. Findings suggestive of overweight, insulin resistance, low insulin secretion, dyslipidemia, and mild intra-abdominal obesity were present. Islet cell antibodies and sequence variants in MODY1 to -6 genes were absent. CONCLUSIONS: Large families demonstrating multigenerational inheritance of diabetes and other characteristics consistent with early-onset type 2 diabetes are present in the Jamaican population.

Clinical features of spontaneous hypothyroidism in one physician's practice in Jamaica.

OBJECTIVE: To describe the clinical characteristics of patients with spontaneous hypothyroidism, the frequency of chronic autoimmune thyroiditis, and the thyroid autoantibody most often associated with this condition in a referral population in Jamaica. METHODS: A retrospective study of all cases referred to the author's endocrinology practice from 1995 to 2005 with a diagnosis of spontaneous hypothyroidism was undertaken. The clinical history, examination findings, biochemical test results, thyroid autoimmune antibodies, and imaging data were reviewed. RESULTS: Spontaneous primary hypothyroidism was correctly diagnosed in 53 subjects. Fifty of the patients were females and three were males. Mean age was 43.3 years (range 12-82 years); 24.4% of the patients had a family member with thyroid disease; 27.1% presented because of a goiter; and 54.2% because of symptoms suggestive of hypothyroidism. The thyroid was palpable in 56.3% and thyroid ultrasound was consistent with Hashimoto's thyroiditis on 64% of occasions. Only 8% of the patients had the atrophic variant of hypothyroidism. Antithyroid peroxidase and antithyroglobulin antibody were positive in 75.8% and 37.5% of patients, respectively. Chronic autoimmune thyroiditis was confirmed in 78.8% of cases. CONCLUSION: In these cases in Jamaica, spontaneous hypothyroidism was predominantly a female disorder. Chronic autoimmune thyroiditis was the commonest cause, and antithyroid peroxidase antibody was the thyroid antibody most likely to be positive in this population.

Multigenerational inheritance and clinical characteristics of three large pedigrees with early-onset type 2 diabetes in Jamaica / Herencia multigeneracional y características clínicas de la diabetes tipo 2 de inicio temprano en tres árboles genealógicos grandes de Jamaica

OBJECTIVE: To document the existence and clinical characteristics of three large families with multigenerational inheritance of early-onset type 2 diabetes in Jamaica. METHODS: Three probands from large families with multigenerational inheritance of early-onset type 2 diabetes in at least three generations were detected at the University Hospital of the West Indies in Jamaica. Each proband at the time of diagnosis was < 25 years of age, was lean, and did not require insulin therapy. Clinical, metabolic, and genetic assessments were undertaken to profile the diabetes in the three families. RESULTS: Three pedigrees-BK, SU, and CA-consisting of 38, 48, and 113 members, respectively, with multigenerational inheritance of early-onset type 2 diabetes in at least three generations, were investigated. The mean age at diagnosis of the three pedigrees was 31.5 ± 2.9 years, with 10 persons detected below 25 years of age. Findings suggestive of overweight, insulin resistance, low insulin secretion, dyslipidemia, and mild intra-abdominal obesity were present. Islet cell antibodies and sequence variants in MODY1 to -6 genes were absent. CONCLUSIONS: Large families demonstrating multigenerational inheritance of diabetes and other characteristics consistent with early-onset type 2 diabetes are present in the Jamaican population.

OBJETIVO: Documentar la presencia de herencia multigeneracional de la diabetes de tipo II de inicio temprano en tres familias jamaiquinas grandes y describir sus características clínicas. MÉTODOS: En el Hospital Universitario de West Indies en Jamaica, se detectaron tres probandos de familias grandes en las que se observó herencia multigeneracional de la diabetes tipo 2 de inicio temprano en al menos tres generaciones. Al momento del diagnóstico, cada probando tenía # 25 años de edad, era delgado y no necesitó insulinoterapia. Se emprendieron estudios clínicos, metabólicos y genéticos con el fin de determinar las características particulares de la diabetes que presentan estas tres familias. RESULTADOS: Se investigaron tres árboles genealógicos -BK, SU y CA- conformados por 38, 48 y 113 miembros, respectivamente. Cada árbol presentaba herencia multigeneracional de diabetes tipo 2 de inicio temprano en al menos tres generaciones. En los tres árboles genealógicos, la media de la edad al momento del diagnóstico fue de 31,5 ± 2,9 años y 10 personas tenían menos de 25 años. Se observaron signos indicativos de sobrepeso, resistencia insulínica, baja secreción de insulina, dislipidemia y obesidad intrabdominal leve. No se hallaron anticuerpos contra las células de los islotes ni variantes en la secuencia de los genes MODY1 a MODY6. CONCLUSIONES: Algunas familias grandes de la población jamaiquina presentan herencia multigeneracional de la diabetes y otras características indicativas de diabetes tipo 2 de inicio temprano.

The burden of gestational diabetes mellitus in Jamaican women with a family history of autosomal dominant type 2 diabetes.

OBJECTIVES: To determine if Jamaican women of African descent with a family history of early onset autosomal dominant type 2 diabetes have greater odds of developing gestational diabetes mellitus (GDM) than those without a family history of the disease. METHODS: A comparative study was conducted of two groups of pregnant Jamaican women: the first with a family history of early onset autosomal dominant type 2 diabetes; the second with no history of the disease. Incidence, odds for developing GDM, and metabolic profiles in first and second trimesters were assessed using SPSS 11.5 (SPSS Inc., Chicago, Illinois, United States). RESULTS: The incidence of GDM was 12.0% in women with a family history of early onset autosomal dominant type 2 diabetes and 1.5% in women without a family history of the disease (P<0.05). Women with a family history were nine times more likely to develop GDM than those without a family history of diabetes (95% confidence interval: 5.00-16.38, P<0.0001). CONCLUSION: Family history of early onset autosomal dominant type 2 diabetes appears to increase susceptibility to GDM in Jamaican women. Pregnant women of any age with family history of early onset autosomal type 2 diabetes should be screened for GDM.

The burden of gestational diabetes mellitus in Jamaican women with a family history of autosomal dominant type 2 diabetes

OBJECTIVES: To determine if Jamaican women of African descent with a family history of early onset autosomal dominant type 2 diabetes have greater odds of developing gestational diabetes mellitus (GDM) than those without a family history of the disease. METHODS: A comparative study was conducted of two groups of pregnant Jamaican women: the first with a family history of early onset autosomal dominant type 2 diabetes; the second with no history of the disease. Incidence, odds for developing GDM, and metabolic profiles in first and second trimesters were assessed using SPSS 11.5 (SPSS Inc., Chicago, Illinois, United States). RESULTS: The incidence of GDM was 12.0 percent in women with a family history of early onset autosomal dominant type 2 diabetes and 1.5 percent in women without a family history of the disease (P < 0.05). Women with a family history were nine times more likely to develop GDM than those without a family history of diabetes (95 percent confidence interval: 5.00–16.38, P < 0.0001). CONCLUSION: Family history of early onset autosomal dominant type 2 diabetes appears to increase susceptibility to GDM in Jamaican women. Pregnant women of any age with family history of early onset autosomal type 2 diabetes should be screened for GDM.

The burden of gestational diabetes mellitus in Jamaican women with a family history of autosomal dominant type 2 diabetes

OBJECTIVES: To determine if Jamaican women of African descent with a family history of early onset autosomal dominant type 2 diabetes have greater odds of developing gestational diabetes mellitus (GDM) than those without a family history of the disease. METHODS: A comparative study was conducted of two groups of pregnant Jamaican women: the first with a family history of early onset autosomal dominant type 2 diabetes; the second with no history of the disease. Incidence, odds for developing GDM, and metabolic profiles in first and second trimesters were assessed using SPSS 11.5 (SPSS Inc., Chicago, Illinois, United States). RESULTS: The incidence of GDM was 12.0 percent in women with a family history of early onset autosomal dominant type 2 diabetes and 1.5 percent in women without a family history of the disease (P < 0.05). Women with a family history were nine times more likely to develop GDM than those without a family history of diabetes (95 percent confidence interval: 5.00-16.38, P < 0.0001). CONCLUSION: Family history of early onset autosomal dominant type 2 diabetes appears to increase susceptibility to GDM in Jamaican women. Pregnant women of any age with family history of early onset autosomal type 2 diabetes should be screened for GDM.

OBJETIVOS: Determinar si las mujeres jamaicanas de ascendencia africana con antecedentes familiares de inicio temprano de diabetes autosómica dominante tipo 2 tienen mayor probabilidad de desarrollar diabetes mellitus gestacional (DMG) que las que no tienen esos antecedentes familiares. MÉTODOS: Se realizó un estudio comparativo con dos grupos de mujeres jamaicanas embarazadas: el primero con mujeres que tenían antecedentes familiares de inicio temprano de diabetes autosómica dominante tipo 2 y el segundo con mujeres sin antecedentes familiares de esa enfermedad. Se empleó el programa SPSS v. 11.5 (SPSS Inc., Chicago, Illinois, Estados Unidos de América) para analizar los resultados y calcular la incidencia, la probabilidad de desarrollar DMG y los perfiles metabólicos en el primer y el segundo trimestres de gestación. RESULTADOS: La incidencia de DMG fue de 12,0 por ciento en las mujeres con antecedentes familiares de inicio temprano de diabetes autosómica dominante tipo 2 y de 1,5 por ciento en las mujeres sin antecedentes familiares de esa enfermedad (P < 0,05). Las mujeres del primer grupo tuvieron nueve veces más probabilidades de desarrollar DMG que las del segundo grupo (intervalo de confianza de 95 por ciento: 5,00 a 16,38; P < 0,0001). CONCLUSIÓN: Los antecedentes familiares de inicio temprano de diabetes autosómica dominante tipo 2 aumentaron la predisposición a sufrir DMG en mujeres jamaicanas. Las mujeres embarazadas con antecedentes familiares de inicio temprano de diabetes autosómica tipo 2 deben someterse a pruebas de tamizaje para DMG, independientemente de su edad.

Diabetes and psychological co-morbidity in children with a family history of early-onset type 2 diabetes.

The present study was conducted to evaluate for depressive symptoms and undiagnosed diabetes in children with familial history of early-onset type 2 diabetes. Studies have shown that diabetes doubles the risk for depression and that the duration of diabetes is related to the severity of the depression. Individuals with depression are also said to be at greater risk for developing diabetes. In many cases diabetes is detected whilst screening for depression. Fifty-three children aged between 6 and 17 years were screened for diabetes and assessed for depressive symptoms using the Children Depression Rating Scale, revised version (CDRS-R). Thirty-six (68.0 %) of the children with a family history of early-onset type 2 diabetes had CDRS-R scores consistent with likely or very likely major depressive disorders. Depressive symptoms score was predicted best by the number of generations of diabetes in the family, with an associated r = .65 and adjusted R(2) = .41. As the generations of diabetes increased, the more likely it was for a child to have diabetes (r = .38, p = .005). Four (7.5%) of the children were diagnosed with diabetes. The findings suggest that depressive symptoms are common in children with a family history of early onset type 2 diabetes and may co-exist with diabetes. The independent variable that reliably predicted the child depressive symptoms score was the number of generations of diabetes in the family.

Depressive symptoms in children of women with newly diagnosed type 2 diabetes.

OBJECTIVE: Type 2 diabetes is a chronic disease with increasing prevalence. Individuals with diabetes are at risk for long-term complications such as nephropathy, retinopathy, and cardiovascular complications. Additionally, several studies have indicated that diabetes doubles the risk for depression. Individuals with depression are also said to be at greater risk for developing diabetes. Studies have shown depressive symptoms to be higher in children with diabetes than in those without the disease. This study measured depressive symptoms in children without diabetes of women with recently diagnosed type 2 diabetes. METHOD: Fifty children whose mothers were newly diagnosed with type 2 diabetes were assessed with the Children's Depression Rating Scale, Revised (CDRS-R) to measure the psychological impact of the mothers' newly diagnosed diabetes on their children. This cross-sectional study was conducted in public and private clinics from April 2001 to June 2003. RESULTS: Sixty percent of children (N = 30) whose mothers were recently diagnosed with type 2 diabetes had CDRS-R scores consistent with likely or very likely having major depressive disorders. Mean ± SD CDRS-R scores were highest in children of women with diabetes affecting greater than or equal to 3 generations of their families (68.2 ± 8.9, p = .02). CONCLUSION: The findings suggest that depressive symptoms are common in children of women with newly diagnosed type 2 diabetes. Severity of depressive symptoms positively correlated with the number of generations of diabetes in the family.

A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity.

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.

Knowledge, beliefs, practices, blood pressure and blood glucose control in women with diabetes mellitus [abstract]

OBJECTIVE: To determine the knowledge, beliefs, practices, blood pressure and blood glucose control among women with diabetes mellitus attending a specialist medical clinic. METHOD: A 43-item pre-tested questionnaire was administered to a purposive sample of 28 (26.4 percent) of women attending the University Hospital of the West Indies Diabetes Clinic in May/June 2001. Weight (wt), height (ht), blood pressure (BP), fasting blood glucose (FBG) and two hour post-prandial blood glucose (2hpp), diet and activity were recorded. Body mass index (BMI, wt/ht2) was calculated. RESULTS: Median age of 57 years, range, 21-85 years; median time since diagnosis was 14.5 years, range, 0.5-51 years. Only 27 percent of patients had BP controlled to ó135/85 mm/Hg. There was an association between systolic BP and BMI (r= 0.43, p<0.05). The majority of the patients were inactive, overweight or obese: median BMI, 30.3 kg/m2. The majority did not follow a diabetic diet and had no recent contact with a dietitian. There was an association between reported intake of sucrose and 2hpp (r= 0.75, p<0.001). The majority (82 percent) did not take alcohol; 14 percent smoked cigarettes. Only 28.6 percent were controlled to FBG ó 8 mmol/l and 2 hpp ó10 mmol/l. Sixty-seven percent of the patients were on insulin; 21.3 percent used a glucometer. Medications were missed a median of two days per month. There were inverse associations between years since diagnosis and number of days per month that medications were missed (r= -0.39, p<0.05) and knowledge scores and age (r= -0.47, p<0.01). There were associations between knowledge, practice and educational level (p<0.01). The doctor was the main source of information. The majority reported having had ECG (57 percent), blood cholesterol and renal function tests (64 percent) in the past year. The majority (57 percent) reported never having had a foot examination; 32 percent reported never having had an eye examination. CONCLUSION: The majority of these patients were inactive and obese with limited control of blood glucose and blood pressure. Although fairly compliant with medication, there was little adherence to therapeutic guidelines regarding diet, exercise and maintenance of normal weight. Closer attention should be given to foot and eye examinations for early detection of complications. Closer monitoring and counselling of patients in these areas is recommended. (AU)

A clinico-pathological study of Cushing's syndrome at the University Hospital of the West Indies and a review of literature

Cushing's syndrome is an uncommon but important disease. Twenty-one confirmed cases of spontaneous Cuching's syndrome were documented at the University Hospital of the West Indies over a 21-year period. They were predominantly young females (F:M ratio of 17:4; mean age 25 years and three months). The commonest presenting symptoms were amenorrhoea (41 percent) and obesity (19 percent). Common clinical features were cushingnoid features (95 percent), hypertension (76 percent) and hirsutism (82 percent). Twenty-nine per cent had frank hyperglycaemia. Cushing's syndrome was due to Cushing's disease in 10 cases, adrenal adenoma in 3 and adrenal carcinoma in 2 cases. In 4 cases with presumed adrenal hyperplasia, the histology was either unavailable or was not consistent with the diagnosis. Two cases appear now to have had ectopic ACTH syndrome. Adrenalectomy was the commonest treatment offered. There were no intra-operative or post-operative deaths but recurrence was common after subtotal adrenalectomy in Cushing's disease. Twenty-seven per cent of the patients developed Nelson's syndrome, which was fatal in 50 per cent. Long-term hormone replacement therapy was unnecessary after surgery for adrenal adenomas. Treatment of Cushing's syndrome was well tolerated by the patients. (AU)

The medical management of diabetes mellitus with particular reference to the lower extremity: the Jamaica experience

Predisposing factors for the diabetic foot include peripheral neuropathy, peripheral vascular disease (PVD), hyperglycaemia and increased duration of diabetes. From the records of patients admitted to the University Hospital of the West Indies with the diabetic foot, we reviewed the results of the microbiology of wound swabs from diabetic foot ulcers. We noted the high prevalence of PVD (66.6 percent), peripheral neuropathy (50 percent), hyperglycaemia (75.6 percent) and increased duration of diabetes (17.5 years). A history of past foot ulcers was common and 87.2 percent had polymicrobial infection. The commonest organisms were gram positive organisms which were usually sensitive to the 2 antibiotic regimes that were commonly used. Euglycaemia, a favourable lipid profile, control of blood pressure, yearly foot examination and institution of measures to prevent foot trauma are important in the prevention of foot ulceration.(Au)