Diabetes mellitus is divided into type 1 (T1DM) and type 2 (T2DM). T1DM is characterized by the destruction of pancreatic beta cells, requiring exogenous insulin for treatment. T2DM is typically a result of insulin resistance and some degree of beta cell deficiency. At some point, patients with T2DM may need exogenous insulin to maintain their blood glucose levels.

Currently, obesity-associated T2DM is a global epidemic. It is characterized by insulin resistance caused by lipotoxicity, hyperinsulinemia, and inflammatory cytokines produced by adipose tissue. T2DM often coexists with obesity, insulin resistance, hypertension, and coronary artery disease, which together are known as the metabolic syndrome.

The major symptoms of diabetes mellitus include high blood glucose levels, frequent urination, excessive thirst, increased appetite, muscle wasting, electrolyte depletion, and ketoacidosis (in T1DM).

Poorly controlled diabetes can lead to long-term complications due to excessive intracellular glucose, particularly in the retina, kidney, and peripheral nerves. This can result in retinopathy, nephropathy, and neuropathy.

Adipose tissue plays an endocrine role, especially in terms of energy homeostasis. It produces hormones such as leptin and adiponectin. Leptin acts on the hypothalamus to promote satiety.

The regulation of serum calcium is influenced by the parathyroid gland, which secretes parathyroid hormone (PTH). The calcium-sensing receptor plays a role in the regulation of PTH secretion.

The production of 1,25-dihydroxyvitamin D involves the precursor of vitamin D, its hydroxylation sites, and key regulators. Vitamin D metabolites are transported in the blood.

PTH targets various organs and affects the mobilization or handling of calcium and phosphate at each site.

Upon completion of this chapter, students should be able to:
1. Describe the pool of serum calcium and phosphate, including ionized, complexed, and protein bound forms. Discuss the normal concentration ranges of these ions and their major influx and efflux routes.
2. Explain the role of the parathyroid gland in regulating serum calcium and the involvement of the calcium-sensing receptor in PTH secretion.
3. Describe the production of 1,25-dihydroxyvitamin D, including the sources of vitamin D precursor, sites and key regulators of vitamin D hydroxylation, and the transport of vitamin D metabolites in the blood.
4. List the target organs of PTH and describe its effects on calcium and phosphate mobilization or handling at each of these sites.
5.
Diabetes mellitus is classified as type 1 (T1DM) and type 2 (T2DM). T1DM is characterized by destruction of pancreatic beta cells, and exogenous insulin is required for treatment. T2DM can be due to numerous factors but is usually characterized as insulin resistance coupled to some degree of beta cell deficiency. Patients with T2DM may require exogenous insulin at some point to maintain blood glucose levels.
19. Obesity-associated T2DM is currently at epidemic proportions worldwide and is characterized by insulin resistance due to lipotoxicity, hyperinsulinemia, and inflammatory cytokines produced by adipose tissue. T2DM is often associated with obesity, insulin resistance, hypertension, and coronary artery disease. This constellation of risk factors is referred to as the metabolic syndrome.
20. Major symptoms of diabetes mellitus include hyperglycemia, polyuria, polydipsia, polyphagia, muscle wasting, electrolyte depletion, and ketoacidosis (in T1DM).
21. The long-term complications of poorly controlled diabetes are due to excess intracellular glucose (glucotoxicity), especially in the retina, kidney, and peripheral nerves. This leads to retinopathy, nephropathy, and neuropathy.
Bailey CJ, et al. Future glucose-lowering drugs for type 2 diabetes. Lancet Diabetes Endocrinol. 2016;4:350-359.
Davidson JA, et al. Glucagon therapeutics: dawn of a new era for diabetes care. Diabetes Metab Res Rev. 2016;doi:10.1002/dmrr.2773; [Epub ahead of print].
Font-Burgada J, et al. Obesity and cancer: the oil that feeds the flame. Cell Metab. 2016;23:48-62.
22. Adipose tissue has an endocrine function, especially in terms of energy homeostasis. Hormones produced by adipose tissue include leptin and adiponectin. Leptin acts on the hypothalamus to promote satiety.
Klein MS, Shearer J. Metabolomics and type 2 diabetes: translating basic research into clinical application. J Diabetes Res. 2016;2016:3898502. doi:10.1155/2016/3898502; [Epub 2015 Nov 9].
Marion-Letellier R, et al. Fatty acids, eicosanoids and PPAR gamma. Eur J Pharmacol. 2016;785:44-49.
Pawlak M, et al. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in nonalcoholic fatty liver disease. J Hepatol. 2015;62:720-733.
Upon completion of this chapter the student should be able to answer the following questions: 1.
Describe the pool of serum calcium and phosphate, including ionized, complexed, and protein bound. Describe the normal concentration ranges of these ions and the major routes of influx and efflux.
2.
Discuss the role of the parathyroid gland in the regulation of serum calcium and explain the role of the calcium-sensing receptor in the regulation of parathyroid hormone (PTH) secretion.
3.
Describe the production of 1,25-dihydroxyvitamin D, including sources of vitamin D precursor, sites and key regulators of vitamin D hydroxylation, and transport of vitamin D metabolites in the blood.
4.
List the target organs of PTH and describe its effects on calcium and phosphate mobilization or handling at each of these sites.
5.