Recently, cluster analysis has been proposed to classify adult onset diabetes which can better predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. We evaluated the application of this classification in a VA diabetes clinic. Ninety patients who had C-peptide and anti-GADab, and detailed clinical follow-up, were included in the analysis. Additionally we defined patients with severe insulin resistance as those who required > 200 units of insulin a day and those with insulin doses < 0.5 U/kg/day were categorized as mild insulin resistance. Six subjects belonged to the Severe Autoimmune Diabetes (SAID) cohort, with average GADab 713±301IU; 66% of the cohort had nephropathy, 33% had retinopathy. The Severe Insulin Deficiency (SIDD) cohort had 9 patients, of which 4 had retinopathy, 3 had nephropathy. Thirty subjects had severe insulin resistance (n=30, M/F=29/1 age 61±2 yr), duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U) and 32 had mild insulin resistance (N=32, M/F: 28/2, age 61±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Insulin resistant subjects had a higher BMI, (41 ± 2 vs. 30 ±1 kg/m2, p<0.05), and higher plasma triglyceride (325±0.3 vs. 202±0.3 mg/dl, p=0.04). Prevalence of nephropathy was higher in the insulin resistant group vs. the mild insulin resistant group (76% vs. 43%, p<0.05). There was no difference in prevalence of retinopathy (p=0.09) or CAD (p=0.6) between the groups. Our results support the higher prevalence of diabetic nephropathy in patients with severe insulin resistance. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications. Disclosure J. Trejo: None. S. Pinkson: None. L. Gondin: None. L. Esteve: None. X. Chen: None. D. Tripathy: None.

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Background: Long-term effects of gender-affirming hormonal therapy (GAHT) on cardiovascular risk factors and metabolic syndrome (MS) is currently unclear. Particularly, the effect of GAHT on cardiovascular outcomes in older individuals (>60 years) with gender dysphoria (GD) is unknown. The aim of this study was to examine the effect of GAHT on cardiovascular risk factors, MS and the incidence of T2DM in subjects with GD. Methods: We reviewed the records of 75 subjects with GD, 54 transwomen (age 49 ± 2 years) and 21 transmen (age 37 ± 2 years), who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA 1C , FPG, testosterone, estradiol) of which 55 were followed for at least 1 year. MS was defined based on ATP III criteria. As a control group, we reviewed the records of 30 subjects without GD who attended the endocrinology clinic for other hormone-related disorders. Results: The median (IR) follow-up was 22 (11-39) months for transwomen and 15 (11-21) months for transmen. In transwomen plasma testosterone levels decreased (379 ± 31 vs 71 ± 18 ng/dL), estradiol increased (40 ± 7 vs 124 ± 34 pg/mL) while the plasma testosterone levels increased in transmen (57 ± 14 vs 411 ± 79 ng/dL). At baseline, 24% of transwomen had MS and after 1 year, 16% of subjects had MS. In transmen, the prevalence of MS was similar before and 1 year after treatment (25 % vs. 24%). In transwomen, GAHT was associated with mild weight gain, BMI increased (29 ± 1 vs. 30 ± 1 kg/m 2 , p=0.04). There was no difference in HDL, total cholesterol and triglyceride levels before and after hormone therapy, though LDL cholesterol tended to decrease (101 ± 6 vs. 90 ± 6 mg/dL, p=0.06). There was no change in HbA 1C , FPG or SBP in transwomen, though DBP decreased (77 ± 1 vs. 74 ± 1 mmHg, p=0.05). In transmen, no changes were observed in BMI, HDL, total cholesterol, triglycerides, LDL, HbA 1C , FPG and blood pressure. There were no new cases of T2DM, however 1 transman developed MS, 1 transman had CABG and 1 transwoman died from laryngeal cancer. There were no new cases of myocardial infarction or stroke in subjects with and without GD. For subjects above 60 years (n=16, 13 transwomen and 3 transmen), BMI in transwomen increased (27 ± 1 vs. 29 ± 2 kg/m 2 , p=0.03), there was no change in HDL, LDL and total cholesterol, triglycerides, HbA 1C , FPG or blood pressure. In 3 transmen older than 60 years old, only the LDL decreased (194 ± 59 vs. 141 ± 55 mg/dL, p=0.006). In the entire group as well as older individuals with GD the incidence of CV events were not different from the control group. Conclusion: GAHT for 1.5 years was not associated with worsening cardiovascular risk factors, metabolic syndrome or incidence of T2DM in both transmen and transwomen regardless of their age. Long-term stud...

Gender affirming hormone therapy (GAHT) is the mainstay of long-term management of transgender individuals. In transwomen, treatment with physiologic doses of estrogen alone is often insufficient to suppress testosterone to the desired level. Although GnRH agonist therapy is usually prescribed for puberty suppression in trans youth, in adult transwomen, GnRH agonist may be added. The durability of long-term GnRH agonist in lowering testosterone as well as the long-term safety is not clear. We examined the effect of leuprolide a GnRH agonist, on testosterone as well as clinical and metabolic features in transwomen Veterans. Out of 91 subjects with gender dysphoria followed at a VA Endocrinology clinic, 65 were transwomen (age 49 ± 3 years) who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol). We performed a retrospective cohort study of the 31 (48%) transwomen on Leuprolide (3.375mg q month) and 33 transwomen who were not on Leuprolide. Plasma testosterone, lipid profile, were analyzed before, 6 months, 1 year and at the last follow-up visit. The median follow-up of subjects on Leuprolide was 2.7 (1.7-3.8) years. Plasma testosterone concentration declined by 89% from 432±32 ng/dl to 47±9 ng/dl within 3-6 months after initiation of GnRH agonist treatment. Plasma testosterone remained persistently low 39±4ng/dl at 1 year and at the end of 2.7 yrs, most subjects on Leurprolide had plasma testosterone concentration <50ng/dl. Leuprolide therapy led to similar rapid decline in testosterone concentration in both younger (<40yrs) or relatively older (>50yr) transwomen. Leuprolide was in general well tolerated requiring discontinuation in just one patient due to severe fatigue. Three subjects (10%) experienced hot flashes which did not lead to discontinuation of medication. In the non-Leuprolide group, of 33 subjects, the follow-up was relatively inconsistent and only 12 subjects were regularly followed throughout a year with stable treatment. The decline in plasma testosterone was of a lower magnitude versus the leuprolide group (55% vs 89%, p <0.05). The testosterone levels declined from 393±42 to 180±44 ng/dl at 6 months. Body weight, and lipid profile: triglyceride, and plasma HDL concentration did not change significantly with or without GnRH agonist therapy. In conclusion, GnRH agonist therapy led to a sustained suppression of plasma testosterone levels in transwomen and was not associated with worsening lipid profile, was effective, and well tolerated in transwomen regardless of their age and may be considered an adjunct to the ant-androgen and estrogen therapy.

Recently, cluster analysis has been used to classify adult onset diabetes based on pathophysiologic profile. Using autoimmunity status, BMI, insulin resistance, and beta cell function, this classification system can predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. Clinically, patients with severe insulin resistance can be defined as those who require high doses of insulin to achieve glycemic control, such as patients on U-500 insulin requiring more than 200 units of insulin a day. To characterize the clinical and metabolic phenotype of insulin-resistant patients from a South Texas VA diabetes clinic, we evaluated presence of macro or microvascular complications and beta-cell autoimmunity and function in this population. A retrospective cohort study was completed at the South Texas VA Diabetes Clinic. Charts were reviewed for anthropometric measurements, presence of macro and microvascular complications, anti-diabetic medication, lipid profile and HbA1c over 3 visits, autoimmunity (anti-GADab), and beta-cell function (fasting C-peptide). Patients with insulin doses >200 U/day or on U-500 insulin were categorized as “severe insulin-resistant”. Those with insulin doses < 0.5 U/kg/day were categorized as “mild insulin resistance” as a control group. Out of 120 patients, 30 met criteria for severe insulin resistance (n=30, M/F=29/1 age 61±1.6 years (yr), BMI 41±0.9 kg/m2, duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U). 30 patients with insulin use <0.5 U/kg/day met criteria for mild insulin resistance (N=30, M/F: 28/2, age 62±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Prevalence of nephropathy was higher in the insulin resistant group vs the mild insulin resistant group (76% vs 43%, p<0.05). There was no difference in prevalence of retinopathy (p=0.095) or CAD (p=0.6) between the groups. There was no difference in use of ACE-i or SGLT-2i between the groups. Insulin resistant subjects had a higher plasma triglyceride (325±0.3 vs 202±0.3 mg/dl, p=0.04). Prevalence of GAD ab was not different between the groups (3% vs 0%). Fasting C-peptide concentrations were similar in both groups (5.6±0.3 vs 5.2±0.25 ng/ml, p=0.3). HbA1c in the insulin resistant group improved between visits 1 and 3 (p<0.01). Weight increased over three visits in the severe insulin resistant group as opposed to mild weight loss in the mild insulin resistant group. Our results support the high prevalence of diabetic nephropathy in patients with severe insulin resistance, although it is unclear that insulin resistance is the etiology. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications.