Real-world effectiveness of osteoporosis treatment in the oldest old.

We studied effectiveness of osteoporosis treatment in women older than 80 years, who often are not included in clinical trials. Treatments were as effective on bone density and fractures as in younger women. INTRODUCTION: To study real-world effectiveness of osteoporosis treatment on BMD and fractures in the oldest old women (≥ 80 years) compared with women (60-79 years) in the clinical setting using Swedish health register data. METHODS: National registers and data from DXA machines were used to study effectiveness of all available osteoporosis treatments in women 60-79 and ≥ 80 years using three approaches: (1) Total Hip BMD change up to 8 years after treatment start; (2) fracture incidence where patients served as their own controls, comparing the first 3 months after treatment start with the subsequent 12 months; and (3) comparison of fracture incidence post-fracture in women ≥ 80 years treated with osteoporosis treatment or calcium/vitamin D. RESULTS: Analysis 1: Total Hip BMD increased by up to 6.7% and 7.7% in women 60-79 and ≥ 80 years old, respectively. The mean increase in BMD was 1.1%-units per year in both age groups. Analysis 2: Relative to the 3-month baseline, fracture incidence decreased during the subsequent 12 months of treatment. Incidence rate ratios were estimated at 0.65, 0.74, 0.29, and 0.81 for any, hip, vertebral, and non-hip-non-vertebral fracture, respectively. Analysis 3: A 24-month incidence of any fracture in women ≥ 80 years given post-fracture osteoporosis treatment was lower (HR = 0.78) than in women given calcium/vitamin D, but treatment allocation was not random, with lower mortality (HR = 0.51) in patients receiving OP treatment. CONCLUSIONS: Osteoporosis medication in women > 80 years in clinical practice likely works, and the magnitude of effect is similar to what was estimated in younger women. The choice between osteoporosis treatment and calcium/vitamin D after fracture in women ≥ 80 years is not random but appears associated with the patient's health status and presence of vertebral fractures, rather than the known risk profile of sustaining a fracture at a high age.

Dual energy 4D-CT of parathyroid adenomas not clearly localized by sestamibi scintigraphy and ultrasonography - a retrospective study.

PURPOSE: At present, the gold standard for diagnosing PAs includes ultrasonography of the neck and sestamibi scans of the parathyroid. The objective of this study was to evaluate scans performed in 4D-DECT (4D-dual-energy mode) at three different time points, in order to analyze spectral information from PAs, lymph nodes (LNs), and thyroid gland (Thy). METHOD: Fifteen patients (mean age: 57 ± 18.9 years) with primary hyperparathyroidism, in which previous ultrasound and sestamibi scanning proved to be negative or equivocal, underwent 4D-DECT in three different phases. Hounsfield units (HU), dual-energy information (electron density [Rho], atomic number [Z], dual-energy index [DEI]), and spectral information (keV) were determined. RESULTS: For all energies, PAs exhibited significantly lower HU-values than the Thy in non-contrast images, and higher HU-values than LNs in the arterial phase (p < 0.05). All three tissues differed significantly in HU in the venous phase at 90 kV, 150 kV, and mixed 0.8 images; the Thy showed significantly higher HU-values than PAs or LNs in non-contrast images at 90 kV, 150 kV, mixed 0.8 images, and [Rho] (p < 0.05). LNs exhibited significantly lower HU-values than PAs and Thy in the arterial phase at 90 kV, 150 kV, mixed 0.8, Rho, Z, and DEI (p < 0.05). With regards to spectral information, lower energies showed greater HU differences between the three tissues. During the venous phase, there were significant differences between all three tissues up to 100 keV (p < 0.05). CONCLUSIONS: We identified significant differences in HU-values and spectral information between PAs, LNs, and Thy at different energies and contrast phases.

Risk of imminent fracture following a previous fracture in a Swedish database study.

This study examined the imminent risk of a future fracture within 1 and 2 years following a first fracture in women aged 50 years and older and assessed independent factors associated with risk of subsequent fractures. The study highlights the need to intervene rapidly after a fracture to prevent further fractures. INTRODUCTION: This study aims to determine the imminent risk of subsequent fractures within 1 and 2 years following a first fracture and to assess independent factors associated with subsequent fractures. METHODS: Retrospective, observational cohort study of women aged ≥ 50 years with a fragility fracture was identified from Swedish national registers. Clinical/demographic characteristics at the time of index fracture and cumulative fracture incidences up to 12 and 24 months following index fracture were calculated. Risk factors for subsequent fracture were identified using multivariate regression analysis. RESULTS: Two hundred forty-two thousand one hundred eight women (mean [SD] age 74 [12.5] years) were included. The cumulative subsequent fracture incidence at 12 months was 7.1% (95% confidence interval [CI], 6.9-7.2) and at 24 months was 12.0% (95% CI, 11.8-12.1). The rate of subsequent fractures was highest in the first month (~ 15 fractures per 1000 patient-years) and remained steady between 4 and 24 months (~ 5 fractures/1000 patient-years). Higher age was an independent risk factor for imminent subsequent fractures (at 24 months, sub-distribution hazard ratio [HR], 3.07; p < 0.001 for women 80-89 years [reference 50-59 years]). Index vertebral fracture was a strong independent risk factor for subsequent fracture (sub-distribution HR, 2.72 versus hip fracture; p < 0.001 over 12 months; HR, 2.23; p < 0.001 over 24 months). CONCLUSIONS: Our findings highlight the need to intervene rapidly after any fragility fracture in postmenopausal women. The occurrence of a fragility fracture provides healthcare systems with a unique opportunity to intervene to reduce the increased risk of subsequent fractures.

A health economic simulation model for the clinical management of osteoporosis.

The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. INTRODUCTION: The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. METHODS: The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines. RESULTS: The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382-3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient). CONCLUSIONS: The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats.

The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4+/-0.2 (vehicle) vs. 2.9+/-0.5 g (H3), P<0.001; ARC 0.7+/-0.3 (vehicle) vs. 2.7+/-0.2 g (H3), P<0.05; and APOA 0.8+/-0.1 (vehicle) vs. 2.2+/-0.2 g (H3), P<0.05]. Cumulative food intake was significantly increased

Ghrelin cell density in the gastrointestinal tracts of animal models of human diabetes.

Ghrelin cell density in the gastrointestinal tract of animal models of human diabetes type 1 and 2 was investigated. The animals used were non-obese diabetic (NOD) mice and obese diabetic mice. Ghrelin cells were detected by immunohistochemistry and quantified by computerized image analysis. Ghrelin-immunoreactive cells were detected in all animals studied. They were abundant in the oxyntic mucosa, patchy and few in the duodenum and rare in the colon. The density of ghrelin-immunoreactive cells decreased in diabetic, pre-diabetic NOD mice and in obese diabetic mice as compared to controls, though not statistically significant. It was concluded that the reduced density of ghrelin-immunoreactive cells in animal models of human diabetes type 1 and 2 might explain the slow gastric emptying and slow intestinal transit found in diabetes gastroenteropathy.

Effect of diabetic state on co-localization of substance P and serotonin in the gut in animal models.

Changes in the numbers of serotonin- and substance P-immunoreactive (IR) cells occur in several animal models of diabetes. It is not known, however, whether these changes are a result of actual cell loss or are caused by modified gene expression in cells showing co-localization of serotonin and substance P. The pattern of mono- and co-expression of serotonin, as well as of substance P, was therefore investigated in gastrointestinal endocrine cells from animal models of human type 1 and type 2 diabetes, namely non-obese diabetic (NOD) and obese diabetic (ob/ob) mice. Immunocytochemical staining by the avidin-biotin complex method was performed for computerized image analysis of each cell type, and by immunofluorescence double staining to study co-localization. Tissues from antrum, proximal duodenum and distal colon were investigated. Co-localization of serotonin- and substance P-IR was found in all investigated parts of the gut. In antrum, substance P immunoreactivity was found exclusively in serotonin-IR cells. In both NOD and ob/ob mice there was a reduced number of substance P-IR cells, but an unchanged serotonin-IR cell count, which thus tallies with a shut-off of substance P expression in antral enterochromaffin cells. In duodenum, both diabetes models showed a decreased number of serotonin-IR cells. Furthermore there was a decreased number of substance P-IR cells in the type 2 model. The proportion of serotonin-IR cells showing substance P-immuno-reactivity was decreased in both diabetic models, thus indicating a shut-off of substance P-gene expression. However, this does not fully explain the changes in duodenum, but the diabetic state probably affects the number of mono-expressed cells as well. In colon, no change was found in diabetic mice regarding co-localization of substance P and serotonin. However, pre-diabetic NOD mice showed a decreased proportion of substance P in serotonin-IR cells, which might be explained by the increased number of serotonin-IR cells, combined with an unchanged number of substance P-IR cells. In conclusion, diabetic animal models of both type 1 and type 2 appear to have a combination of decreased expression of substance P in serotonin-IR cells of both antrum and duodenum, as well as a change in the number of mono-expressed cells. The pattern in colon, on the other hand, seems to be unaffected.

Myenteric plexus of obese diabetic mice (an animal model of human type 2 diabetes).

The myenteric plexus of the gastrointestinal tract was investigated in the obese diabetic mouse, an animal model of human type 2 diabetes. Sections were immunostained by the avidin-biotin complex method, using a general nerve marker, protein gene product 9.5 (PGP 9.5), as well as antibodies to several important neurotransmitters. Computerized image analysis was used for quantification. When diabetic mice were compared with controls, no difference was found in the density of PGP 9.5-immunoreactive (IR) nerve fibres in antrum, duodenum or colon. In antrum and duodenum, diabetic mice showed a decreased number of vasoactive intestinal peptide (VIP)-IR neurons in myenteric ganglia as well a decreased relative volume density in myenteric plexus (though not significantly in antrum, p=0.073). No difference was found regarding VIP-IR nerves in colon. The volume density of nitric oxide synthase (NOS)-IR nerve fibres was decreased in antrum and duodenum of diabetic mice, whereas no difference was found in colon. The density of galanin-IR nerve fibres was decreased in duodenum. Whereas neuropeptide Y (NPY)- and vesicular acetylcholine transporter (VAChT)-IR nerve fibres was increased in density in colon of diabetic mice, no difference was found in antrum and duodenum. Regarding substance P, there was no difference between diabetic and control mice in antrum, duodenum or colon. The present study shows that gut innervation is affected in this animal model of human type 2 diabetes. It is possible that the present findings may have some relevance for the gastrointestinal dysfunctions seen in patients with type 2 diabetes.

Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes.

Gastrointestinal symptoms in diabetic patients are commonplace, and are believed to be due, at least partly, to neuropathy of the gut. In the present study, therefore, some important neurotransmitters in the myenteric plexus were investigated in non-obese diabetic mice, an animal model of human type 1 diabetes. For this purpose, immunocytochemistry was applied on sections from antrum, duodenum and colon, subsequently quantified by computerized image analysis. Whereas the number of vasoactive intestinal peptide (VIP)-positive neurons was increased in antral myenteric ganglia of diabetic mice, there was a decreased density of nerve fibres in muscularis propria. No difference was seen in the VIP of duodenum and colon. Acetylcholine-containing nerve fibres showed an increased volume density in muscularis propria of antrum and duodenum, but a decreased density in colon of diabetic mice, as compared with controls. There was a decreased number of neurons containing nitric oxide synthase (NOS) in myenteric ganglia of antrum and duodenum. No difference was seen in density of NOS-containing nerve fibres in muscularis propria. There was no difference regarding neuropeptide Y (NPY) and galanin between diabetic and control mice; nor was there any difference between pre-diabetic NOD mice and controls regarding all bioactive substances investigated. It is concluded that the diabetic state affects the innervation of gut in this animal model. The present findings may be of some relevance to the gastrointestinal symptoms seen in patients with diabetes.

Does diabetic state affect co-localization of peptide YY and enteroglucagon in colonic endocrine cells?

BACKGROUND: Changes in the numbers of PYY- and enteroglucagon-immunoreactive cells in colon of animal models of human diabetes have been reported. As these peptides co-localize in the same cells it is possible that the observed changes are a result of changes in co-localization. METHODS: Animal models of human type 1 and type 2 diabetes, namely the non-obese diabetic (NOD) mouse and the obese (ob/ob) mouse, were studied. As controls for the NOD mice, BALB/cJ mice were used and for ob/ob mice, homozygous lean (+/+) mice were used. Tissue samples from colon were double-immunostained for PYY and enteroglucagon according to the indirect immunofluorescence method. RESULTS: Co-localization of enteroglucagon and PYY was found in colonic endocrine cells in all groups investigated. Compared with controls, pre-diabetic NOD mice showed a decreased proportion of enteroglucagon/PYY co-localization. There was no difference in diabetic NOD mice or diabetic ob/ob mice when compared with controls. CONCLUSIONS: Whereas the number of cells containing solely enteroglucagon and solely PYY increases in pre-diabetic NOD mice, production of enteroglucagon in PYY-immunoreactive cells decreases. Although the numbers of PYY and enteroglucagon cells have been reported to be changed in both diabetic NOD mice and in obese mice, the balance between co-expressing and mono-expressing cells seems to be preserved.

Gastrointestinal endocrine cells in an animal model for human type 2 diabetes.

Endocrine cells were investigated in various parts of the gastrointestinal tract in an animal model for human type 2 diabetes, namely the homozygous obese mouse. As controls, age- and sex-matched homozygous lean mice were used. The different endocrine cell types were stained by using immunocytochemistry and quantified by computerized image analysis. The numbers of PYY- and enteroglucagon-immunoreactive (IR) cells were decreased in the colon of obese diabetic mice vis-à-vis controls. Serotonin-IR cells were significantly decreased in numbers in the duodenum and colon. Furthermore, colonic serotonin cells had a high cell secretory index (CSI), but an unchanged nuclear area, indicating an impaired cellular release of this amine. There was no statistical difference between obese diabetic mice and lean controls regarding the numbers and CSI of antral gastrin/CCK-, somatostatin- and serotonin-; and duodenal secretin-, gastric inhibitory peptide (GIP)-, CCK/gastrin-, and somatostatin-IR cells; nor was there any difference regarding nuclear area, with the exception of the antral somatostatin- and duodenal GIP-IR cells. It is concluded that the abnormalities in gut endocrine cells observed in the present study might explain the gut dysmotility reported in animal models for human diabetes. They may also be of importance in gastrointestinal dysfunction occurring in diabetes patients.

Prevalence of gastrointestinal symptoms in young and middle-aged diabetic patients.

BACKGROUND: Gastrointestinal disorders have been reported in patients with diabetes mellitus. The present investigation was carried out to evaluate the frequency of gastrointestinal symptoms in out-clinic diabetic patients in the county of Umeå, Sweden. METHODS: Diabetic patients aged 24-59 years residing in Umeå County (population, 136,000) were included in the study (n = 489), as were 200 sex- and age-matched healthy controls. A questionnaire was mailed to the patients and controls, and a reminder was sent 5 months later. The questionnaire contained 28 questions concerning gastrointestinal symptoms, bowel habits, and medication during the preceding year. RESULTS: Fifty-nine per cent of the patients and 53% of the controls responded. The total number of reported gastrointestinal symptoms was significantly greater in patients (1.25 +/- 0.10; mean +/- standard deviation) than in control subjects (0.50 +/- 0.08). This increase was seen in both type-1 (1.12 +/- 0.11) and type-2 (1.52 +/- 0.25) diabetic patients. Female diabetic patients reported significantly more symptoms than did male patients (1.59 +/- 0.17 and 0.81 +/- 0.12, respectively). Patients with neuropathy had significantly more symptoms than the other patients. Symptom frequency was not correlated with nephropathy or retinopathy or with the duration of diabetes, body mass index, glycosylated haemoglobin, or insulin dose. Heartburn, constipation, and nocturnal urge to defecate were significantly more frequent in patients than in controls. Furthermore, a feeling of incomplete defecation, a need to strain at defecation, and urgency were significantly more common in patients. CONCLUSION: Diabetic patients had more gastrointestinal symptoms than non-diabetic population. These symptoms did not correlate with duration of the disease, metabolic control, or any other complication except neuropathy. Heartburn and constipation were among the symptoms that occurred more frequently in diabetic patients than in the non-diabetic population.

Myenteric plexus in the gastrointestinal tract of non-obese diabetic mice.

The myenteric plexus was investigated in the gastrointestinal tract of pre-diabetic and diabetic non-obese diabetic (NOD) mice. The plexus was immunostained by the avidin-biotin complex method, using a general marker for nerve elements, namely protein gene-product 9.5. The nerve fibres were quantified by point-counting and the number of ganglia and their area were determined by image analysis. The relative volume density of the nerve fibres in duodenal muscularis propria was found to be significantly reduced in of both pre-diabetic and diabetic NOD mice. There was no statistical difference between controls and NOD mice regarding relative volume density of nerve fibres in antral and colonic muscularis propria. The number of myenteric ganglia/mm baseline was significantly decreased in the duodenum of diabetic NOD mice, and showed a non-statistically significant tendency to decrease in pre-diabetic mice. In the antrum and colon, there was no difference between the controls and NOD mice regarding the number of ganglia/mm baseline. Nor was there any significant difference between controls and NOD mice in the area of myenteric ganglia in either antrum, duodenum or colon. It is concluded that the changes in the duodenal myenteric plexus of NOD mice are prior to the onset of diabetes. It is suggested that the absence of changes in the antral and colonic myenteric plexus when using a general marker for neuroelements does not preclude a possible change in cholinergic, adrenergic or peptidergic innervation.

Abnormalities of small intestinal endocrine cells in non-obese diabetic mice.

The endocrine cells in the duodenum of pre-diabetic and diabetic female non-obese diabetic (NOD) mice aged 22-24 weeks were studied by means of immunohistochemistry and computed image analysis as well as by radioimmunoassays of tissue extracts. As controls, 12 female BALB/cJ mice of the same age as NOD mice were used. The number of secretin-immunoreactive cells increased in diabetic but not in pre-diabetic NOD mice. The level of extractable secretin was higher in both pre-diabetic and diabetic NOD mice. The number of GIP-, CCK/gastrin-, and serotonin-immunoreactive cells was significantly reduced in both pre-diabetic and diabetic NOD mice. There was no statistical difference in the number of somatostatin-immunoreactive cells between the NOD mice and controls. The level of GIP was higher and gastrin was lower in NOD mice compared to controls. There was no statistical difference in the somatostatin level between the NOD mice and controls. The cell secretory index was elevated in all the endocrine cell types except CCK/gastrin cells. It has been suggested that some of the changes in the duodenal endocrine cells could be attributed to the diabetes state, but most of the changes seem to take place before the onset of diabetes. The abnormalities in the duodenal endocrine cells observed here in an animal model for diabetes type I might have relevance for the gastrointestinal dysfunction displayed in human diabetes.

Neuropeptide contents in the duodenum of non-obese diabetic mice.

Twelve pre-diabetic and 12 diabetic female NOD mice aged 22-24 weeks were studied. As controls, 12 female BALB/cJ of the same age and sex were used. The duodenal content of several neuropeptides, namely vasoactive intestinal polypeptide (VIP), neurotensin, neuropeptide Y (NPY), galanin, gastrin-releasing peptide (GRP) and enkephalin was determined by radioimmunoassay of tissue extracts. The VIP content in duodenal extracts from both pre-diabetic and diabetic NOD mice was significantly higher than that of the controls. The enkephalin content of the duodenum of diabetic mice was significantly higher than that of the controls, while no significant difference was found between the controls and pre-diabetic mice. There was no statistically significant difference between controls and NOD mice regarding the duodenal content of neurotensin, NPY, galanin or GRP. It has been suggested that the high duodenal content of VIP appears to be primary to the onset of diabetes and that the high enkephalin content may be attributable to the diabetic state. The changes in the duodenal content of VIP and enkephalin reported here in an animal model for diabetes type I might be of relevance for the gastrointestinal complications occurring in human diabetes.

Substance P in the gastrointestinal tract of non-obese diabetic mice.

BACKGROUND: Gut dysmotility occurs in most diabetics. Substance P is a neurotransmitter that plays an important role in regulating gastrointestinal motility. The present investigation was carried out to evaluate the possible role of this neurotransmitter in the pathogenesis of dysmotility in diabetics. METHODS: Pre-diabetic and diabetic female non-obese diabetic (NOD) mice aged 22-24 weeks were studied. As controls, BALB/CJ mice of the same age and sex were used. Substance P concentrations in tissue extracts from the antrum, duodenum, and colon were determined with radioimmunoassay. Substance P-immunoreactive nerve elements and endocrine cells were identified by immunocytochemistry and quantified with computerized image analysis. RESULTS: Substance P levels in the antrum of both pre-diabetic and diabetic NOD mice were significantly lower than those of controls. In the duodenum and colon substance P levels were higher than those of the controls in both pre-diabetics and diabetic NOD mice. The relative volume density of substance P-immunoreactive nerve fibres in the colon of diabetic NOD mice was significantly decreased. There was no statistically significant difference between pre-diabetic and diabetic NOD mice and controls with regard to the relative volume density of substance P immunoreactive nerve fibres in the antrum and duodenum. In the antrum the number of substance P-immunoreactive cells decreased significantly in both pre-diabetic and diabetic NOD mice. In the duodenum and colon the numbers of these cells in NOD mice did not differ from those of controls. CONCLUSIONS: The changes in substance P contents in various parts of the gastrointestinal tract of NOD mice seem to be primary to the onset of diabetes. The decreased antral substance P contents in NOD mice seems to be caused by structural change in the mucosal endocrine cells. In the small and large intestine the increase in substance P levels appears to be caused by change in the physiologic activities of the nerve element and/or endocrine cells rather than by structure changes. The abnormalities observed here in an animal model for diabetes type I might have relevance for the gastrointestinal dysmotility displayed in human diabetes.

Antral endocrine cells in nonobese diabetic mice.

The antral endocrine cells were investigated in nonobese diabetic (NOD) mice by means of immunohistochemistry, image analysis, and radioimmunoassays (RIA). As controls BALB/CJ mice of the same age and sex as the NOD mice were used. The number of gastrin- and somatostatin-immunoreactive cells was significantly decreased in both prediabetic and diabetic mice. There was no statistical difference between the NOD mice and controls regarding the serotonin-immunoreactive cells. Somatostatin levels as revealed by RIA in the antrum of both prediabetic and diabetic NOD mice were lower than those of the controls. There was no statistical difference in the level of antral gastrin between NOD mice and the controls. It was concluded that the changes in antral cells are primary to the onset of diabetes, and that the abnormalities observed in the antral cells in an animal model for diabetes type I might have relevance for the upper gastrointestinal dysfunction displayed in human diabetes.

Large intestinal endocrine cells in non-obese diabetic mice.

Colonic endocrine cells from prediabetic and diabetic non-obese diabetic mice as well as of the sister strain, BALB/cJ, were investigated by immunocytochemistry and computer image analysis. In prediabetic mice, enteroglucagon-and serotonin-immunoreactive cells were significantly increased in number, whereas the cell secretory index of these two cell types was significantly reduced. No significant differences were found in numbers or cell secretory index of peptide YY (PYY)-immunoreactive cells. In diabetic mice, PYY-immunoreactive cells were significantly fewer, but there were no significant differences in the numbers of enteroglucagon-and serotonin-immunoreactive cells. Whereas the cell secretory index was reduced in serotonin-producing cells, no significant differences were found between diabetic and control mice regarding the cell secretory index of PYY- and enteroglucagon-immunoreactive cells. Nor was any statistically significant difference found between controls, prediabetic and diabetic non-obese diabetic mice, regarding the thickness of submucosa, of circular and longitudinal-muscle layers, or of the mucosal area/microm baseline. The present study showed that abnormalities in colonic endocrine cells do occur, in both prediabetic and diabetic mice, but they are different in nature and can be divided into primary and secondary to the diabetes onset. The present findings of abnormal colonic endocrine cells in non-obese diabetic mice, an animal model for human insulin-dependent diabetes mellitus, might help explain the gastrointestinal disorders observed in patients with diabetes. The study also showed that the change in the colonic endocrine cells is dynamic and started before the onset of the diabetic condition.