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Aims: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations. Methods: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM). Results: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years. Conclusions: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM.

Publisher Summary This chapter discusses the molecular analysis of the parathyroid hormone (PTH) gene and parathyroid hormone-related peptide receptor (PTHrP). The human PTH gene is a single-copy gene that extends over 4200 basepairs of DNA on the short arm of chromosome 11. The gene contains three exons, the first of which is noncoding. The second exon contains the initiator ATG and encodes all of the signal or pre-sequence and most of the short pro-peptide. The third exon encodes the remainder of the pro-sequence, the residues corresponding to the mature hormone, as well as the 3′ noncoding region. PTH/PTHrP receptors from marsupial kidney and from kidney and bone of two mammalian species, human and rat, are highly homologous. PTH and PTHrP bind with equal affinity to similar, perhaps identical, receptors in kidney and bone. PTH/PTHrP receptors stimulate adenylate cyclase with the same efficacy when activated by either ligand or are capable of activating at least two effector molecules, adenylate cyclase and phospholipase C. PTH/PTHrP receptors have significant homology only with the calcitonin and the secretin receptor and little or no similarities with other G protein-linked receptors. These three receptor types represent the first members of a novel family of G protein-linked receptors.