Latent autoimmune diabetes of adulthood: case report

Abstract Background Primary care clinicians will see a higher incidence of type 2 diabetes in adult patients, and the diagnosis and management of an initial presentation of type 1 diabetes can pose challenges to clinicians who see it less frequently. Symptoms of hyperglycemia and risk of ketoacidosis may be missed. Further, endocrine autoimmune disease can run together in patients and families. Case presentation A 49-year-old Caucasian female with history of pituitary adenoma and Graves’ disease with history of thyroid ablation presented in the outpatient setting due to hand tingling of her right middle finger that was worse in the mornings and improved throughout the day. She also complained of excessive thirst, finding herself drinking more water than usual and waking up in the night to urinate. There was no dysuria or haematuria, and no other neurologic symptoms. She did report feeling hungry. She had no family history of diabetes, normal body mass index of 21.7, and reported taking her thyroid replacement medication every day. The differential diagnosis for her thirst included dehydration, psychogenic polydipsia, diabetes mellitus, diabetes insipidus, and anxiety. The patient had normal vital signs and was well appearing; labs were ordered for her on her way home from clinic with no medications. Labs revealed a random blood glucose level of 249 mg/dL, normal renal function, a normal B12 of 996 pg/mL, and an elevated thyroid stimulating hormone level of 25.67 u[iU]/mL. On follow up with her primary care provider 5 days later, additional labs were drawn showing A1C of 11.5%, 1+ ketonuria, a negative Acetest, and a normal basic metabolic panel, except for a fasting glucose of 248 mg/dL, and Free T3 of 2.42 pg/mL, and Free T4 of 1.7 ng/dL. Islet cell antibodies and glutamic acid decarboxylase antibodies were both positive, consistent with type 1 diabetes. She was started on insulin and improved. Conclusion Given the patient’s age, this is a less common presentation of type 1 diabetes mellitus, as a part of polyglandular autoimmune syndrome type IIIa. It serves as a reminder that clinicians should remember that patients with one autoimmune disease (in this case, h/o Graves’ disease) are at higher risk for diabetes and other endocrine autoimmune diseases and should be screened appropriately. Clinicians should keep latent type 1 diabetes in the differential in adulthood to ensure proper and timely treatment

Latent autoimmune diabetes of adulthood: case report

Abstract Background Primary care clinicians will see a higher incidence of type 2 diabetes in adult patients, and the diagnosis and management of an initial presentation of type 1 diabetes can pose challenges to clinicians who see it less frequently. Symptoms of hyperglycemia and risk of ketoacidosis may be missed. Further, endocrine autoimmune disease can run together in patients and families. Case presentation A 49-year-old Caucasian female with history of pituitary adenoma and Graves’ disease with history of thyroid ablation presented in the outpatient setting due to hand tingling of her right middle finger that was worse in the mornings and improved throughout the day. She also complained of excessive thirst, finding herself drinking more water than usual and waking up in the night to urinate. There was no dysuria or haematuria, and no other neurologic symptoms. She did report feeling hungry. She had no family history of diabetes, normal body mass index of 21.7, and reported taking her thyroid replacement medication every day. The differential diagnosis for her thirst included dehydration, psychogenic polydipsia, diabetes mellitus, diabetes insipidus, and anxiety. The patient had normal vital signs and was well appearing; labs were ordered for her on her way home from clinic with no medications. Labs revealed a random blood glucose level of 249 mg/dL, normal renal function, a normal B12 of 996 pg/mL, and an elevated thyroid stimulating hormone level of 25.67 u[iU]/mL. On follow up with her primary care provider 5 days later, additional labs were drawn showing A1C of 11.5%, 1+ ketonuria, a negative Acetest, and a normal basic metabolic panel, except for a fasting glucose of 248 mg/dL, and Free T3 of 2.42 pg/mL, and Free T4 of 1.7 ng/dL. Islet cell antibodies and glutamic acid decarboxylase antibodies were both positive, consistent with type 1 diabetes. She was started on insulin and improved. Conclusion Given the patient’s age, this is a less common presentation of type 1 diabetes mellitus, as a part of polyglandular autoimmune syndrome type IIIa. It serves as a reminder that clinicians should remember that patients with one autoimmune disease (in this case, h/o Graves’ disease) are at higher risk for diabetes and other endocrine autoimmune diseases and should be screened appropriately. Clinicians should keep latent type 1 diabetes in the differential in adulthood to ensure proper and timely treatment

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors