Reviews & Analysis

The global burden of microvascular disease associated with type 2 diabetes mellitus continues to escalate. Furthermore, conventional standards of care do not completely abolish the risk of diabetic retinopathy, nephropathy or neuropathy in affected individuals. In this Review, the authors highlight the issue of residual microvascular risk and discuss intensive treatment with statins and/or fibrates to target atherogenic dyslipidemia, a potential trigger of the microvascular complications that can develop in patients with type 2 diabetes mellitus.

Much attention has focused on the increasing prevalence of childhood type 2 diabetes mellitus. However, considerable evidence suggests that the incidence of childhood type 1 diabetes mellitus is also increasing. The results of a multicenter registration study from Europe confirm this alarming trend, which has important health-care implications.

Vitamin D deficiency is widespread among women with breast cancer. Guidelines currently recommend daily supplementation with 400 IU vitamin D₃; however, attainment of a circulating level of 25-hydroxyvitamin D defined as sufficient (that is, ≥75 nmol/l) might not be possible with this level of supplementation, according to data published in the Journal of Clinical Oncology.

Diabetes mellitus is associated with cognitive decrements and alterations on brain imaging. However, important questions remain concerning risk factors and mechanisms for cerebral damage in patients with this condition. Data from two new studies shed new light on the relationship between hypoglycemia and cognitive dysfunction in older people with type 2 diabetes mellitus.

Numerous risk-group stratification, staging and scoring systems exist to stratify patients with differentiated thyroid cancer into prognostic risk groups that guide patient management decisions. The tumor–node–metastasis staging system is the most widely adopted despite its relative complexity, but could a simplified, quantitative alternative to the system provide superior prognostic value?

Charcot arthropathy of the neuropathic foot and ankle is characterized by bone and joint destruction and deformities that may lead to ulcer, soft tissue infection, osteomyelitis and amputation. This article reviews the evaluation and treatment of this condition, highlighted by a clinical case of a man with type 2 diabetes mellitus who had Charcot collapse of the longitudinal arch, rocker bottom deformity and plantar ulcer.

Biochemical control cannot be achieved by the use of somatostatin analogs alone in a large number of patients with acromegaly. Combination therapy with somatostatin analogs and the growth-hormone-receptor antagonist pegvisomant is, however, highly effective at normalizing levels of insulin-like growth factor I. In this Review, the efficacy and safety of somatostatin analog–pegvisomant combination therapy as a potential tool for the medical management of patients with acromegaly is discussed.

The Diabetes Control and Complications Trial (DCCT) was a landmark study that evaluated intensive versus conventional insulin therapy in patients with type 1 diabetes mellitus; the Epidemiology of Diabetes Interventions and Complications (EDIC) study continues to follow the same cohort of patients. Many of the key contributions that the DCCT and EDIC have made to our understanding of type 1 diabetes mellitus are discussed by the authors of this Review.

Early foundations of the metabolic syndrome may be laid as a consequence of changes in dietary supply to the rapidly growing fetus and/or postnatal offspring. This review highlights fetal developmental plasticity in cellular homeostasis that may manifest in adult life as the metabolic syndrome particularly if followed by a period of accelerated postnatal growth.

This review discusses newly recommended screening approaches for childhood acute malnutrition in low-income settings, using mid-upper arm circumference or weight for height Z-score and inspection for presence of bipedal edema. A treatment algorithm is provided to guide management of children with severe acute malnutrition and systemic complications who require inpatient therapy and for those with uncomplicated severe or moderate acute malnutrition who can be treated in the community using recently developed ready-to-use-therapeutic foods or other appropriately designed food blends.

Despite the increasing implementation of iodization programs, benign nodular thyroid disease will remain a prevalent therapeutic concern for decades. Recent research suggests that nonsurgical therapy, including radioactive iodine, radiofrequency thermal ablation and percutaneous laser ablation, might have a role in the treatment of symptomatic patients.

A question often asked by health-care providers is whether metformin has added benefits if continued after patients with type 2 diabetes mellitus switch to insulin. Beneficial effects on macrovascular end points observed in response to sustained metformin therapy argue in favor of this approach, according to new research from The Netherlands.

Intensive insulin therapy is extensively used to lower blood glucose concentrations in critically ill patients hospitalized within the intensive care unit. The discovery by the NICE-SUGAR study investigators that tight glucose control in this setting might actually increase mortality has generated considerable discussion about the wisdom of this approach.

Uncertainty exists about the best approach to manage levothyroxine dosage in women with hypothyroidism, once they become pregnant. The etiology of an individual's hypothyroidism might be a key determinant of the optimal time and duration of dose adjustments, say the authors of a retrospective review published in the journal Thyroid.

Exposure of the fetus to low levels of thyroid hormones for extended periods during pregnancy can lead to irreversible brain damage and potential delays in neurological and behavioral development. What are the exact mechanisms behind this abnormality, and can prompt initiation of maternal iodine supplementation prevent this adverse effect?

Knowledge of the epidemiology, natural history, diagnosis, treatment, and rates of recurrence of nonfunctioning pituitary adenomas has greatly improved over the past few years. Wass and Karavitaki now highlight some of these advances and speculate on future avenues of research. In addition, they describe their own experience in the clinical management of patients with nonfunctioning pituitary adenomas.

Congenital adrenal hyperplasia (CAH) is a disorder of cortisol biosynthesis that is usually caused by a mutation in the gene that encodes steroid 21-hydroxylase. As this abnormality can lead to fatal shock, hyponatremia and hyperkalemia in early infancy, many countries include tests for CAH in their neonatal screening program. The author of this article provides an overview of the currently used methodologies for neonatal CAH screening and discusses their efficiency, limitations and cost-effectiveness.

Aromatase deficiency is an extremely rare syndrome that is characterized by congenital estrogen deprivation. Early diagnosis is a key consideration, and estrogen therapy should be initiated as soon after puberty as possible in order to avoid the skeletal complications associated with this disorder. Here, Rochira and Carani review the presentation, diagnosis and treatment of aromatase deficiency in men.

Mutations in a number of genes have been identified in patients as the primary genetic cause of idiopathic hypogonadotropic hypogonadism. These genes encode proteins that regulate gonadotropin-releasing hormone (GnRH) neuron development, migration from the nasal placode to the hypothalamus, GnRH secretion or GnRH action. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in idiopathic hypogonadotropic hypogonadism.

Very little is known about how the changes in body composition that occur around the time of menopause might affect subsequent risk of new-onset diabetes mellitus, as well as the management of pre-existing disease, in postmenopausal women. Here, Emily D. Szmuilowicz and colleagues discuss the potential relationship between menopause, diabetes mellitus and the use of postmenopausal hormone therapy.