Diagnosis and Treatment > Medication
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Summary
Mutations in hepatocyte nuclear factor 1β gene (HNF1B) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations.
Learning points:
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HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.
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The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history may not be present.
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Once diagnosis is made, treatment of diabetes with oral agents is worth trying, since the response can be sustained for a longer period than the one usually described. Oral treatment can help postpone insulinization and, once this is necessary, can help reduce the required doses.
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Search for other papers by Kellie L Spiller in
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Summary
Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin.
Learning points
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Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide.
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Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled.
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Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.
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Summary
Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol.
Learning points
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Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA).
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Sitagliptin administration in patients with LADA might prolong the insulin-free period.
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Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease.
