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Type 1 Diabetes: A Review

Author/s: 
Laura M Jacobsen, Desmond A. Schatz

Importance Type 1 diabetes is defined by hyperglycemia due to autoimmune destruction of the insulin-producing beta cells in the pancreas, leading to insulin deficiency, and accounts for 5% to 10% of all cases of diabetes. Type 1 diabetes affects approximately 2 million people in the US and 8.4 million people worldwide and is associated with microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, and cardiovascular disease.

Observations Ninety percent to 95% of people with type 1 diabetes have at least 1 autoantibody when they are diagnosed with diabetes. These autoantibodies include autoantibodies to insulin, glutamic acid decarboxylase 65, insulinoma-associated 2, and zinc transporter 8 autoantibodies and are absent in type 2 diabetes or monogenic diabetes (a rarer form of diabetes caused by a single genetic variant). These autoantibodies are present before clinical symptoms develop and can identify early stages of type 1 diabetes. Up to 44% of children and 23% of adults with type 1 diabetes present with diabetes-related ketoacidosis. Type 1 diabetes is most commonly diagnosed between ages 10 and 14 years, but the median age of diagnosis in the US is 24 years. People with type 1 diabetes require lifelong insulin replacement, which can be administered via subcutaneous injection or insulin pump. Insulin regimens that mimic normal physiology include long-acting basal insulin (eg, glargine or degludec) administered once to twice daily and rapid-acting bolus insulin (eg, aspart or lispro) administered prior to meals that contain carbohydrates and during periods of hyperglycemia. Randomized clinical trials have demonstrated that continuous glucose monitors with insulin pumps, which automatically adjust insulin delivery in response to glucose levels, result in less hypoglycemia and improved hemoglobin A1c levels (with the greatest improvement occurring in those with higher starting levels [eg, >8.0%]).

Conclusions and Relevance Type 1 diabetes accounts for 5% to 10% of all cases of diabetes and is characterized by the presence of islet autoantibodies in 90% to 95% of patients. Lifelong use of insulin therapy is currently required for treatment of type 1 diabetes.

Keywords 
diabetes type 1 Insulin Therapy Hyperglycemia

Hypothyroidism: A Review

Author/s: 
Layal Chaker, Maria Papaleontiou

Importance: Hypothyroidism is a disease of thyroid hormone deficiency. The prevalence ranges from 0.3% to 12% worldwide, depending on iodine intake, and it is more common in women and older adults. Untreated hypothyroidism can cause serious health complications such as heart failure and myxedema coma.

Observations: Hashimoto thyroiditis (an autoimmune disease) is the cause of primary hypothyroidism in up to 85% of patients with hypothyroidism living in areas with adequate nutritional iodine levels. The risk of developing hypothyroidism is associated with genetic factors (having a first-degree relative with hypothyroidism), environmental factors (iodine deficiency), undergoing neck surgery or receiving radiation therapy, pregnancy in the setting of underlying autoimmune thyroid disease, and with the use of certain medications (eg, immune checkpoint inhibitors and amiodarone). Patients with hypothyroidism may have nonspecific symptoms due to metabolic slowing, including fatigue (68%-83%), weight gain (24%-59%), cognitive issues (45%-48%) such as memory loss and difficulty concentrating, and menstrual irregularities (approximately 23%) such as oligomenorrhea and menorrhagia. Hypothyroidism can cause insulin resistance and hyperglycemia in patients with diabetes, increase the risk for cardiovascular events, such as heart failure, and negatively affect female reproductive health, causing disrupted ovulation, infertility, and increased risk of miscarriage. Untreated hypothyroidism may progress to severe hypothyroidism with decompensation (myxedema coma), which is a condition associated with hypothermia, hypotension, and altered mental status that requires treatment in an intensive care unit and has a mortality rate of up to 30%. Hypothyroidism is diagnosed based on biochemical testing; a high thyrotropin (TSH) level and a low free thyroxine (T4) level indicate overt primary hypothyroidism. Screening for hypothyroidism is not recommended for asymptomatic individuals. Targeted testing is recommended for patients who are considered high risk (eg, patients with type 1 diabetes). First-line treatment for hypothyroidism is synthetic levothyroxine to normalize thyrotropin levels. Initial dosages should be tailored to patient-specific factors. Lower starting doses should be used for older patients or those with atrial fibrillation and coronary artery disease. Thyrotropin monitoring should be performed 6 to 8 weeks after initiating levothyroxine treatment, or when changing the dose, and then annually once the thyrotropin level is at goal to avoid overtreatment or undertreatment, both of which are associated with cardiovascular health risks.

Conclusions and relevance: Hypothyroidism may be associated with fatigue, weight gain, memory loss, difficulty concentrating, cardiovascular disease such as heart failure, menstrual irregularities, infertility, and increased risk of miscarriage. Levothyroxine is the first-line treatment to normalize the thyrotropin level and improve clinical manifestations due to hypothyroidism.

Keywords 
Endocrinology Thyroid Disorders hypothyroidism Reproductive Health

A Review of the Pathophysiology and Management of Diabetes in Pregnancy

Author/s: 
Egan, A.M., Dow, M.L., Vella, A.

Diabetes is a common metabolic complication of pregnancy and affected women fall into two subgroups: women with pre-existing diabetes and those with gestational diabetes mellitus (GDM). When pregnancy is affected by diabetes, both mother and infant are at increased risk for multiple adverse outcomes. A multidisciplinary approach to care before, during, and after pregnancy is effective in reducing these risks. The PubMed database was searched for English language studies and guidelines relating to diabetes in pregnancy. The following search terms were used alone and in combination: diabetes, pregnancy, gestational diabetes, GDM, prepregnancy, and preconception. A date restriction was not applied. Results were reviewed by the authors and selected for inclusion based on relevance to the topic. Additional articles were identified by manually searching reference lists of included articles. Using data from this search we herein summarize the evidence relating to pathophysiology and management of diabetes in pregnancy. We discuss areas of controversy including the method and timing of diagnosis of GDM, and choice of pharmacologic agents to treat hyperglycemia during pregnancy. Therefore, this review is intended to serve as a practical guide for clinicians who are caring for women with diabetes and their infants.

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