Diabetes in Danish bank voles (M. glareolus): survivorship, influence on weight, and evaluation of polydipsia as a screening tool for hyperglycaemia

Abstract

Background: Previous studies have concluded that the development of polydipsia (PD, a daily water intake ≥ 21 ml) among captive Danish bank voles, is associated with the development of a type 1 diabetes (T1D), based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin.

Aim and methods: We retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent.

Results: We found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively.

Conclusion: The relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods.

Figure 1. Survival following onset of polydipsia (PD).

The survival of PD voles (line with open circles; n = 155) are compared with the survival of NN voles (line with filled circles; n = 178) after age 60 days. Each circle signifies an event of “natural death” (90 among PD; 13 among NN). The abscissa denotes ages in days and the ordinate denotes the fraction of survivors.

Figure 2. Weight of polydipsic (PD) and normodipsic (NN) voles.

Weights of male and female PDs (closed circles) and NNs (open circles) through 23 weekly weight measurements at ages 21 days (session “1”) to 170–177 days (session “23”). The number of NNs through sessions 1–23 equals 68, 68, 68, 66, 62, 52, 49*, 49, 46, 46, 45, 45, 42, 39, 39, 39, 38, 36, 34, 32, 30, 29, and 29 (* one female was not weighed because of an error). The corresponding number of PDs equals 0, 0, 0, 2, 4, 14, 16, 17, 20, 20, 18, 15, 17, 15, 9, 7, 6, 4, 2, 2, 2, 2, and 2. The ordinate denotes weight (g) and the abscissa denotes the sessions.

Figure 3. Daily water intake (DWI) correlated with levels of blood glucose (BG) – all voles.

Scattergram of DWI (ml - abscissa) correlated with levels of BG (mg/dl - ordinate). Data from both polydipsic (PD) and normodipsic (NN) voles are used. N = 187.

Figure 4. Daily water intake (DWI) correlated with levels of blood glucose (BG) – only polydipsic (PD) voles.

Scattergram of DWI (ml - abscissa) correlated with levels of BG (mg/dl - ordinate). N = 38.

Figure 5. Daily water intake (DWI) correlated with levels of blood glucose (BG) – only normodipsic (NN) voles.

Scattergram of DWI (ml - abscissa) correlated with levels of BG (mg/dl - ordinate). N = 149.

Figure 6. Levels of blood glucose (BG) correlated with days from onset of polydipsia (PD).

Scattergram of levels of BG (mg/dl - ordinate) and days from onset of PD (abscissa). Only data from polydipsic (PD) voles are used. N = 36.