Weight fluctuation, mortality, and cardiovascular disease in adults in 18 years of follow-up: Tehran Lipid and Glucose Study.

PURPOSE: Controversies exist in the effect of body weight loss and fluctuation on cardiovascular disease (CVD) and mortality. This study aims to assess the effect of weight variability on CVD and all-cause and cardiovascular mortality in the Tehran Lipid and Glucose Study (TLGS) cohort. METHOD: Participants aged ≥ 40 year at the baseline period with at least 3 BMI measurements were included in this study. After excluding individuals with cancer, CVD, end-stage renal disease, systemic use of glucocorticoids, pregnancy, and missing covariates at the baseline, a total of 3461 participants were enrolled and followed for 18 years. BMI variability was defined using root mean squared error (RMSE) and average successive variability (ASV). In the RMSE method, BMI variability was calculated using the best-fitting model for BMI trend of each subject. Multivariate Cox proportional hazard models were applied to assess BMI variability's effect on CVD and mortality. RESULTS: Among the 3461 participants in this study, the group with the highest weight variability had an increased risk of death for all-cause (HR 1.65; 95% CI 1.21-2.25), non-cardiovascular (HR 1.77; 95% CI 1.24-2.53), and non-cancer (HR 1.77; 95% CI 1.25-2.50) mortality. However, BMI variability showed to be protective against CVD (HR 0.76; 95% CI 0.6-0.97). These findings were significant in males, non-smokers, participants with age ≤ 60 year, BMI < 30, negative BMI slope, and both diabetic and non-diabetic subjects. CONCLUSION: High BMI variability is associated with increased risk of all-cause, non-CVD, and non-cancer mortality, although protective for the CVD event. Appropriate strategies for body weight maintenance after weight loss could be adopted to avoid weight variability, particularly in non-obese subjects.

Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS).

OBJECTIVE: The significance of subclinical hypothyroidism (SCH) is largely due to its potential risk for developing overt hypothyroidism (OH). Investigations are still exploring predictive factors contributing to the progression of SCH to OH, particularly in patients with mildly elevated serum thyrotropin (TSH). We aimed to clarify the natural history of SCH and the predictive factors of its progression, based on the grade of SCH severity. METHODS: This study was conducted within the framework of the Tehran Thyroid Study (TTS), in which 5783 individuals aged ≥ 20 years were followed. After applying exclusion criteria, data of 270 SCH subjects remained for the analysis. Thyroid function tests were assessed at baseline and every 3 years. RESULTS: Of 270 participants with SCH, 239 (88.5%) had TSH level between 5.06 and 10 mU/L, and 31 (11.4%) had TSH ≥ 10 mU/L. During a median follow-up of 10 years, 40% had TSH within the reference range, 44% maintained elevated TSH, and 16% had added low T4 to the elevated TSH. The annual incidence rate of progression to OH was 22.3 (16.5-101.9) per 1000 person-years [18 (12.6-25.6) for those with TSH 5.07-9.9 mU/L and 57.8 (22.8-101.9) for patients with TSH ≥ 10 mU/L per 1000 person-years (P = 0.001)]. After adjusting age, sex, body mass index (BMI), thyroid peroxidase antibody (TPOAb), and serum TSH, only TPOAb positivity (HR: 2.31; 95% CI 1.10-4.83, P = 0.026) and baseline TSH level ≥ 10 mU/L (HR: 5.14; 95% CI 2.14-12.3, P < 0.001) remained as predictors for development of OH. In patients with TSH 5.07-9.9 mU/L, TPOAb positivity was associated with an increased risk of OH (HR: 2.41; 95% CI 1.10-5.30, P = 0.027). However, in patients with TSH ≥ 10 mU/L, TPOAb positivity was not a predictor (P = 0.49). CONCLUSION: TPOAb and not TSH are associated with the development of OH in individuals with serum TSH below 10 mU/L, and follow-up at regular intervals is recommended in TPOAb-positive individuals with TSH between 5 and 10 mU/L.

Treatment of post-radioactive iodine relapse of hyperthyroidism: comparison of long-term methimazole and radioactive iodine treatment.

BACKGROUND: This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism. METHODS: Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3 months in the first year and then every 6 months for a total of 60 months. RESULTS: In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6 years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1 months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0 months in the RAI group and 3.5 ± 2.8 months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60 months in the euthyroid state (p < 0.001). CONCLUSION: In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60 months of follow-up.

Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves' disease: a systematic scoping review.

BACKGROUND: Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism. OBJECTIVE: The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years. METHODS: Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. RESULTS: We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24 months versus 6 months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%. CONCLUSION: Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Thyroid dysfunction in patients with impaired glucose metabolism: 11 year follow up from the Tehran Thyroid Study.

OBJECTIVES: This study aimed to assess the prevalence and incidence and predictive factors of thyroid disorders (TD) in patients with impaired glucose metabolism. METHODS: Prevalence of TD was calculated in patients with impaired glucose metabolism compared to healthy controls, aged over 30 years in phase 1 of the Tehran Thyroid Study (TTS). Follow up assessments were conducted every 3 yrs, after which incidence of TD was calculated and its correlations with age, sex, smoking, blood pressure, body mass index (BMI), thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides and cholesterol were assessed. RESULTS: Incidence of TD among 435 diabetics, 286 prediabetics, and 989 healthy controls at baseline was 14, 18, and 21 per 1000 patients per year, respectively, being significantly lower in diabetics than that in healthy controls, a difference however that was not significant after adjusting for the variables mentioned (OR:0.64, 95% CI: 0.39-1.01). The incidence of TD in subjects with baseline serum TSH>1.94 mU/L or TPOAb≥40 IU/ml in all three groups was higher than that in patients with TSH≤1.94 mU/L or TPOAb<40 IU/ml, and remained significant after variable adjustment. Baseline TSH>1.94 mU/L was predictive of TD with 70% sensitivity and specificity. Baseline serum TSH (ROC area: 0.73, 95% CI: 0.68-0.77) had better predictive value than TPOAb (ROC area: 0.65, 95% CI: 0.61-0.69) for developing TD. CONCLUSION: Incidence of TD in type 2 diabetics or prediabetics is not higher than healthy controls. It is however necessary to conduct thyroid tests in patients with TPOAb≥40 IU/ml or TSH>1.94 mU/L.

The Association Between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study.

Several studies have shown an association between overt hypothyroidism and diastolic hypertension. Association between subclinical hypothyroidism and hypertension is a matter of debate. The aim of this study was to examine the association of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure with serum thyroid hormones levels in euthyroid subjects.Data from 4 756 individuals of the Tehran Thyroid study (TTS) without any previously known thyroid disease were analyzed. We divided participants based on TSH tertiles. Serum TSH and free T4 (FT4) concentration, systolic blood pressure (SBP), diastolic blood pressure (BPD) body mass index (BMI) were measured in all subjects.Among 5 786 individuals participated, 4 985 were euthyroid. After implementing exclusion criteria, 4 756 individuals remained of whom 2 122 (44.6%) were male and 2 634 (55.4%) were female. Multiple linear regression analysis revealed no association between TSH levels within reference ranges and blood pressure profile. No significant relationship was observed between TSH levels and systolic or diastolic blood pressure or the mean arterial pressure or pulse pressure in each tertile of TSH. There was a negative association between pulse pressure and TSH in the second tertile (r=- 0.066, p=0.009). Regression analysis showed that FT4 was significantly associated with systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure.No association was found between serum TSH and blood pressure profile in euthyroid subjects. Serum FT4 levels showed a positive association with blood pressure profiles.

Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort.

AIM: The association between insulin resistance and thyroid function in euthyroid subjects has not yet been clarified. This study aimed to investigate the association between thyroid function within the normal reference range and insulin resistance in participants of the Tehran Thyroid Study (TTS). METHODS: This cross-sectional study was conducted within the framework of the TTS. Of 5786 subjects aged ≥ 20 years, 2758 euthyroid subjects free of thyroid disorders, diabetes, chronic kidney disease and cardiovascular disease, and not taking steroids and lipid-lowering agents, were included. Serum concentrations of free thyroxine (FT4) and TSH were measured. The homoeostasis model assessment index for insulin resistance (HOMA-IR) was used to evaluate IR. RESULTS: On linear regression analysis, a negative association was found between serum FT4 levels and HOMA-IR in the model with age, smoking and physical activity (B = -0.09, P < 0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B = -0.06, P < 0.01). In addition, there was a positive association between serum TSH levels and HOMA-IR in both models [with age, smoking and physical activity (B = 0.07, P = 0.006), and age, smoking, physical activity and adjusted for WC (B = 0.05, P = 0.01)] that was not more significant on logistic regression analysis. In women, neither serum FT4 nor TSH levels were associated with HOMA-IR; the prevalence of IR decreased from 27.2 to 19.1 with increasing tertiles of FT4 only in men (P = 0.01). No significant differences were observed in HOMA-IR and its components between thyroid peroxidase antibody (TPOAb)-negative and -positive groups. Also, it was found that metabolically healthy but obese (MHO) subjects had higher levels of TSH than individuals who were MONW (metabolically obese but normal weight; P < 0.01). CONCLUSION: Low FT4 was independently associated with IR in healthy euthyroid Iranian men.

Prevalence of hypothyroidism in patients with dyslipidemia: Tehran Thyroid Study (TTS).

Hypothyroidism is a relatively common endocrine disorder usually accompanied with changes in serum lipid profiles. The purpose of this study was to assess the association between dyslipidemia and hypothyroidism in a population-based study. In this cross-sectional study, 2,315 dyslipidemic patients, aged 20-90 years (mean age: 38.1 ± 13.2 years), were selected from among 5,760 participants of Tehran Thyroid Study and divided into 3 groups, the subclinical hypothyroid, overt hypothyroid, and euthyroid subjects, based on national reference ranges. Serum lipid profiles, free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured in all subjects. In subjects with dyslipidemia and nondyslipidemia, the prevalence of subclinical was 7% and 4.1%, respectively, and for clinical hypothyroidism 3% and 1.2%, respectively. In dyslipidemic subjects, the mean low density lipoprotein-cholesterol (LDL-C) levels differed significantly (p = 0.03) among the overt hypothyroid (144.3 ± 36.1), subclinical hypothyroid (129.3 ± 39.2), and euthyroid (132.7 ± 39.0) groups. In the overt hypothyroid group, mean total cholesterol level was higher than in the normal group, but not significant. There were no differences in median triglycerides (TG) and mean high density lipoprotein-cholesterol (HDL-C) levels among the 3 groups mentioned. After adjusting for age and sex, hypothyroidism was not related to elevated serum lipid profiles in patient with dyslipidemia. In conclusion, there is significant difference in the prevalence of subclinical and clinical hypothyroidism between nondyslipidemic and dyslipidemic subjects; after adjustment for age and sex the presence of dyslipidemia did not predict the presence of hypothyroidism.

Underestimation of thyroid dysfunction risk due to regression dilution bias in a long-term follow-up: Tehran Thyroid Study (TTS).

Thyroid dysfunction is linked with mortality and particular diseases. Intra-individual variability of measured thyroid function parameters may bias its association with outcomes, the so called "regression dilution" bias. Single measurements of thyroid function parameters result in underestimation of real associations between outcome rates with the "usual life-long levels" of the aforesaid parameters. The aim of this study was to examine the intra-individual variability of FT4 and TSH of study cohorts in the Tehran Thyroid Study (TTS) and to investigate the extent of the risk underestimation during the 4 phases (Ph) of TTS, with median follow-up of 4, 7, and 10 years between the Ph2-Ph1, Ph3-Ph1, and Ph4-Ph1 intervals; respectively. We estimated regression dilution ratios (RDRs) by the Rosner method of linear regression of repeated measures for FT4 and TSH. RDR1, RDR2, and RDR3 were obtained by regressing the repeated measures of the aforesaid parameters of the last 3 TTS follow-ups on the baseline measurements. Calculations showed 0.64 RDR1, 0.58 RDR2, and 0.52 RDR3 for TSH; and 0.62 RDR1, 0.57 RDR2, and 0.55 RDR3 for FT4. A single measurement-based risk estimation in the TTS was underestimated for FT4 about 61.2, 76.5, and 80.4%; and for TSH as 55.8, 73.1 and 93% after 4, 7, and 10 years of follow-up; respectively. In conclusion, using only single measurements of TSH and FT4 the association between thyroid function and outcome rates is considerably underestimated, especially after a long follow-up period.

Local versus international recommended TSH references in the assessment of thyroid function during pregnancy.

The aim of this study was to compare the prevalence of subclinical and overt hypothyroidism based on local population-specific reference intervals versus arbitrary cutoffs that are not specific for the population studied or the assay used, during pregnancy in an area of iodine sufficiency. We tested a total of 203 pregnant women in the first trimester of pregnancy, and followed their status in the second and third trimesters. Serum samples from women were assayed for levels of total T4 and T3, FT4I, TSH, TPOAb, and TgAb. Of the 203 women based on our national trimester specific reference ranges of serum TSH and FT4I, 153, 157, and 157 were euthyroid in 3 consecutive trimesters of pregnancy. Accordingly, a total of 23, 12, and 13 had subclinical hypothyroidism in the first, second, and third trimester, respectively. Overt hypothyroidism was detected in 4, 5, and 1 women in the first, second, and third trimesters of pregnancy, respectively. The prevalence of subclinical hypothyroidism was 49, 31, and 34 in each of the trimesters respectively, when TSH>2.5 mIU/l was considered for definition of hypothyroidism in the first trimester, and over 3 mIU/l in the second and third trimesters. Our results showed that using arbitrary cutoff values for TSH instead of population-specific reference intervals may inappropriately increase the rate of subclinical hypothyroidism.

An assessment of the iodine status and the correlation between iodine nutrition and thyroid function during pregnancy in an iodine sufficient area.

BACKGROUND: Iodine as a micronutrient is mandatory for thyroid hormone production and inadequate iodine intakes during pregnancy may result in varying degrees of hypothyroidism affecting pregnancy outcomes adversely. The aim of this study was to evaluate nutritional status and its effects on thyroid function in pregnant women during all trimesters of pregnancy. SUBJECTS/METHODS: In this cohort study, we assessed a total of 203 pregnant women in the first trimester of pregnancy and followed them in the second and third trimesters. They were divided into two groups, group I with urinary iodine excretion (UIE) < 150 µg/l, and group II with UIE ≥ 150 µg/l. Serum samples from women were assayed for levels of total T4, T3, FT4I and thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) only once in each trimester. Urinary iodine concentration was measured three times and the median was considered as UIE in the first trimester, but it was measured only once in the second and third trimesters. RESULTS: The median inter quartile ranges of urinary iodine were 218 (150-276) µg/l, 160 (106-260) µg/l and 145 (88-225) µg/l in the three trimesters of pregnancy, respectively; UIE<150 was observed in 48 (24.1%), 90 (44.8%) and 103 (52.3%) of pregnant women in the three trimesters of pregnancy, respectively. The median (range) of TSH was 1.7 (0.9-2.7) mIU/l, 1.9(1.2-2.7) mIU/l and 1.8 (1.1-2.8) mIU/l in the three trimesters of pregnancy, respectively. There was no correlation between UIE, TSH, TT4, FT4I, T3 and TPOAb in the first and second trimesters, but there was a weak correlation between UIE, TSH, T3 and TgAb in the third trimester. CONCLUSION: In our cohort of pregnant women the iodine intakes were sufficient, and no correlation between urinary iodine concentration and thyroid function tests was found.

Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: a population based study.

BACKGROUND: Current reference values for thyroid function tests are based on data from different ethnicities and geographical areas. The aim of the present study was to determine reference intervals for thyrotropin (TSH) and free T4 (FT4), based on the criteria of the National Academy of Clinical Biochemistry (NACB) in an Iranian population. MATERIAL AND METHODS: This study was conducted within the framework of Tehran Thyroid Study (TTS), an ongoing prospective cohort of 5704 randomly selected individuals, age ≥ 20 yr. A total of 2199 individuals (43.3% male, 56.7% female), based on NACB criteria were included in this study. Reference limit analysis was performed for the negative thyroid peroxidase antibody (TPOAb) group. RESULTS: After applying all exclusion criteria except TPOAb positivity (10.5%), data of 2459 participants remained for analysis. Of these, 953 (43.3%) were males and 1246 (56.7%) were females; the mean ± SD age was 43.53 ± 14.16 yr. The mean ± SD and median+IQR for TSH were 1.77 mU/l ± 1.24 and 1.46 (0.93-2.23) mU/l, respectively. The 2.5th and 97.5th percentiles TSH were 0.32 mU/l and 5.06 mU/l respectively. The mean ± SD and median (IQR) for FT4 for all negative TPOAb subjects were 1.19 ± 0.16 and 1.18 (1.08-1.31) ng/dl respectively. CONCLUSION: Reference ranges for thyroid function tests need to be derived from national databases. This study determined age and sex specific TSH and FT4 reference ranges in a Tehranian population, which could eventually enable clinicians to classify patients more appropriately.

Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines.

The presence of thyroid autoantibodies is relatively high in women of childbearing age. There is evidence that positive thyroperoxidase antibody even in euthyroid women may increase the risk of spontaneous and recurrent pregnancy loss and preterm delivery. However, the evidence is not enough to justify recommendation on the screening of pregnant women for thyroid autoantibodies or LT4 supplementation for reducing maternal or fetal complications. In this paper we reviewed the related evidence and compared the new guidelines of the American Thyroid Association and Endocrine Society with respect to the screening and management of positive thyroperoxidase antibody in euthyroid pregnant women. As there was no major contradiction or disagreement between the two guidelines, either one of two guidelines may be used by clinicians for the appropriate management of thyroid autoimmunity during pregnancy.

Neonatal thyroid status in an area of iodine sufficiency.

BACKGROUND: Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency. METHODS: Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 µg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated. RESULTS: Fifty-two pregnant women (38%) had median UIE<150 µg/l and 86 had (62%) UIE ≥ 150 µg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 µg/l, 97 and 213 µg/l, 93 and 227 µg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles. CONCLUSION: This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

Is HLA-DR6 a protective factor against posttransplantation diabetes mellitus?

BACKGROUND: Posttransplant diabetes mellitus (PTDM) has several pre- and posttransplant risk factors. METHODS: The incidence and risk factors of PTDM were retrospectively evaluated in 2117 kidney allograft recipients from June 1984 to March 2004. Type and dosage of immunosuppressive agents, pretransplant weight and human leukocyte antigen (HLA) phenotypes in PTDM patients were compared with 61 matched controls. RESULTS: Sixty-one cases (2.8%) developed PTDM requiring insulin or oral hypoglycemic therapy, out of which 47.5% were men and 52.5% were women, although only 35% of our overall recipients are women. Onset occurred at a mean of 489 days following transplantation. Patients receiving more than 15 mg/d prednisolone developed PTDM more often than those on less than 15 mg/d (P = .000). Similarly PTDM was more frequent among patients who received more than 300 mg/d cyclosporine compared with those on less than 300 mg/d (P = .015). Mean weight in PTDM cases and controls was 65 +/- 13.4 kg and 57 +/- 13.6 kg, respectively (P = .005). HLA-DR6 was observed in 12.2% of nonaffected subjects but in none of the PTDM group (P = .002). Conversely, HLA-DR8 was seen only in PTDM patients (P = .012). In addition HLA-A26 was more common among PTDM patients (P = .02) and HLA-DR52 more frequent in nonaffected subjects (P = .025). CONCLUSION: Our findings suggest that female sex, dosages of prednisolone and cyclosporine, pretransplant weight, and genetic factors are associated with an increased risk of PTDM. The rate of PTDM appeared to be independent of weight gain in the first year posttransplant. Protection against PTDM may be afforded by HLA-DR6 and possibly HLA-DR52. Conversely and higher incidence of diabetes has been associated with HLA-DR8 and HLA-A26.