Substantial differences in the diagnostic criteria used by diabetes experts.

A survey of twenty diabetologists revealed that they employ diagnostic criteria differing quite substantially. In some populations, including the general population of the United States, these disparities would result in very major differences in the rates of "diabetes." Under certain common circumstances, some diabetologists would classify as normal more than half of the one- and two-hour values considered to be abnormal by other well-qualified diabetologists.

Community screening programs for diabetes?

Considerable uncertainty and disagreement now prevail concerning the utility and priority of community screening programs for diabetes. A large majority of diabetologists believe that substantial benefits attend the early discovery of diabetes. Official statements of the American Diabetes Association support the view that mitigation of hyperglycemia lowers risk of morbidity. Much recent evidence indicates that aggressive early treatment often improves beta-cell function, thereby diminishing the severity of diabetes. Even so, some diabetologists and public health specialists question the practical benefits of community screening programs. Indeed, there is considerable evidence that, as previously performed, results sometimes have not justified costs. This article suggests that, when well designed, community screening is stil justified in some circumstances. To a considerable degree, failures of the past are correctable. The American Diabetes Association should neither approve nor disapprove community screening indisciminately. Affiliate organizations and health departments should be free to examine available evidence and local circumstances and, then, to decide whether to undertake screening programs. More care is needed in planning, executing, and critically evaluating these programs, but there is impressive and mounting evidence supporting the potential utility of the early discovery of diabetes.

Standardization of definition, classification, and reporting in diabetes-related epidemiologic studies.

This working paper reviews some advantages and disadvantages of various alternative definitions and classification schemes. Certain of these alternatives were discussed by an international group of experts on the epidemiology of diabetes. It was recommended by the conferees that the following terms not be used as standard descriptors in epidemiologic reports: juvenile diabetes, juvenile-type diabetes, maturity-onset diabetes of youth (MODY), latent diabetes, subclinical diabetes, clinical diabetes, chemical diabetes, and J-type (Jamaica) diabetes. Alternative ways of describing these conditions were offered. Some, but not all, conferees favored abandonment or modification of the terms "secondary diabetes" and "pancreatic diabetes." Two alternate approaches are described in classification. One is designed to classify all types of cases in a single scheme. In this system each case is described by indices that include etiology and special etiologic concomitants, fatness, severity, type of treatment, and, if present, special or peculiar manifestations, and morbidity. This system makes it possible to classify all cases by mutually exclusive categories. A disadvantage of this scheme is that the number of combinations of classifying indices and subindices is great. Another approach is to classify cases by syndromes, using in each class a mixture of indices (e.g., etiology, severity, fatness, etc.). The conferees failed to reach a consensus in the specifics of this approach. There was considerable disagreement on how certain terms should be defined, whether they should be used, and on the degree of need for specific definitions. These designations included the terms "insulin-dependent," "idiopathic," "insulin-requiring," and "ketosis-prone." The conferees agreed that in either of the two approaches to classification, the prime indices should be those that can be ascertained by ordinary clinical methods. Much progress could be accomplished, even in the absence of international standardized definitions and classification systems, provided that authors keep in mind the need to describe the major characteristics of their cases and define the sense in which they use terms such as insulin-dependent, ketosis-prone, obese, etc.

Absence of a relationship between smoking and diabetic microangiopathy.

The relationship between cigarette smoking and retinopathy and proteinuria was examined in a group of 973 subjects with diabetes. Other variables known to influence the risk of microangiopathy were also measured in a standardized fashion (e.g., duration of diabetes, blood glucose, blood pressure). The characteristics of smokers and nonsmokers were studied in detail. It was therefore possible to take into account the effects of confounding variables on the relationship between smoking and risk of microangiopathy. Associations between smoking and risk of microangiopathies, previously reported in some of the smaller studies, were not confirmed in this larger study.

The role of circulating glucose and triglyceride concentrations and their interactions with other "risk factors" as determinants of arterial disease in nine diabetic population samples from the WHO multinational study.

In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.

Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP).

We have cloned and sequenced a novel cDNA (RPR7) encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). RPR7 was identified by PCR of rat pituitary cDNA, and full-length clones were isolated from a rat olfactory bulb cDNA library. When expressed in COS cells, RPR7 was functionally coupled to increases in intracellular cyclic adenosine monophosphate (cAMP) in response to stimulation by PACAP-38, PACAP-27, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI). The order of potency of these ligands was PACAP-38-PACAP-27 > VIP > PHI, suggesting that the receptor corresponds to the pharmacologically characterised PACAP Type I receptor.

The VIP2 receptor: molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide.

We have cloned and sequenced a cDNA (RPR4) encoding a new member of the secretin/calcitonin/parathyroid hormone (PTH) receptor family. RPR4 was identified by PCR of rat pituitary cDNA, and a full-length clone was isolated from a rat olfactory bulb cDNA library. When RPR4 was functionally expressed in COS 7 cells, cyclic adenosine monophosphate (cAMP) production was stimulated by vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptides (PACAP-38 and PACAP-27) and helodermin, with equal potency. Peptide histidine isoleucine (PHI) and rat growth hormone releasing hormone (rGHRH) also stimulated cAMP production at lower potency. This suggests that RPR4 encodes a novel VIP receptor which we have designated the VIP2 receptor. In situ hybridisation showed that mRNA for this receptor was present mainly in the thalamus, hippocampus and in the suprachiasmatic nucleus.

Sperm penetration into a hyaluronic acid polymer as a means of monitoring functional competence.

The diagnostic significance of sperm penetration assays based on a commercially available hyaluronate preparation (Sperm Select) has been investigated in the male partners of 77 couples characterized by a normal female partner. Sperm penetration into hyaluronate was highly correlated with the ability of the same sperm populations to penetrate bovine cervical mucus and, moreover, depended on the same attributes of semen quality, including the morphology of the spermatozoa, their number, and their motility as reflected by their mean path velocity. Stepwise multiple regression analyses employing these independent variables generated r values of 0.821 to 0.931, depending on the criterion of hyaluronate penetration used; path velocity was consistently the most informative variable according to the standardized regression coefficients. The relationship between hyaluronate penetration and sperm movement was so close that multiple regression equations could be generated that were capable of accounting for up to 76% of the variance in sperm velocity measurements obtained with a computerized image analysis system. Regression equations could also be generated using the hyaluronate penetration data that could account for 65% of the variance observed in an A23187-enhanced zona-free hamster oocyte penetration test, including the successful identification of the subpopulation of patients in whom 0% oocyte penetration had been recorded. Within the same data set, independent variables based on bovine cervical mucus penetration could only account for 43.5% of the variance in sperm-oocyte fusion. Hyaluronate penetration therefore appears to offer a simple, objective means of generating information on the functional competence of human spermatozoa that should find a role in routine diagnostic services where the more specialized tests are not available.