The amended insulin to glucose ratio and diagnosis of insulinoma in dogs

Amended insulin to glucose ratios were calculated from the concentrations of serum insulin and blood glucose measured concurrently during either a glucagon tolerance test or after feeding in healthy dogs. Values greater than 30 𝛍U/mg which are supportive of a diagnosis of insulinoma were obtained at certain times during the test period. Amended insulin to glucose ratios calculated from serum insulin and blood glucose concentrations obtained during a glucagon tolerance test and an oral glucose tolerance test on a dog with an insulinoma were less than 30 𝛍U/mg, or equivocal, at different times during the test period. This indicates that under some circumstances healthy dogs may have elevated amended insulin to glucose ratios, and dogs with insulinoma may have a normal amended insulin to glucose ratio. Care is essential for interpretation of amended insulin to glucose ratios, and a diagnosis of insulinoma using the ratio must be made in conjunction with appropriate clinical signs of hvnoglvcaemia.     

The amended insulin to glucose ratio and diagnosis of insulinoma in dogs

Amended insulin to glucose ratios were calculated from the concentrations of serum insulin and blood glucose measured concurrently during either a glucagon tolerance test or after feeding in healthy dogs. Values greater than 30 microU/mg which are supportive of a diagnosis of insulinoma were obtained at certain times during the test period. Amended insulin to glucose ratios calculated from serum insulin and blood glucose concentrations obtained during a glucagon tolerance test and an oral glucose tolerance test on a dog with an insulinoma were less than 30 microU/mg, or equivocal, at different times during the test period. This indicates that under some circumstances healthy dogs may have elevated amended insulin to glucose ratios, and dogs with insulinoma may have a normal amended insulin to glucose ratio. Care is essential for interpretation of amended insulin to glucose ratios, and a diagnosis of insulinoma using the ratio must be made in conjunction with appropriate clinical signs of hypoglycaemia.     

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.     

Renal clearance, insulin secretion and glucose tolerance in spontaneous diabetes mellitus of dogs.

A standard intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose loads were studied in 14 cases of diabetes mellitus in dogs. In addition, urinary glucose excretion, and clearances of urea, creatinine and phosphate were also determined in these dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half-time (T 1/2) or fractional clearance rate (k-value) and were further classified as Types I, II or III diabetes on the basis of their insulin responses. Renal functional impairment was observed in about 60 percent of the cases and was generally mild. There appeared to be no apparent relationship between advanced chronic renal disease and severity of diabetes in dogs.     

Effects of pre‐operative administration of medetomidine on plasma insulin and glucose concentrations in healthy dogs and dogs with insulinoma

ObjectiveTo investigate the effect of medetomidine on plasma glucose and insulin concentrations in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.AnimalsTwenty–five dogs with insulinoma and 26 healthy dogs.MethodsIn dogs with insulinoma, medetomidine (5 μg kg^?1) was randomly included (n = 12) or omitted (n = 13) from the pre–anesthetic medication protocol, which typically contained an opioid and an anticholinergic. Healthy dogs received medetomidine (5 μg kg^?1; n = 13) or acepromazine (0.04 mg kg^?1; n = 13) plus an opioid (morphine 0.5 mg kg^?1) and an anticholinergic (atropine 0.04 mg kg^?1) as pre–anesthetic medications. Pre–anesthetic medications were given intramuscularly. Plasma glucose and insulin concentrations were measured before (sample 1) and 30 minutes after pre–anesthetic medication (sample 2), and at the end of surgery in dogs with insulinoma or at 2 hours of anesthesia in healthy dogs (sample 3). Glucose requirement to maintain intra–operative normoglycemia in dogs with insulinoma was quantified and compared. Data were analyzed with anova and Bonferroni post–test, t–tests or chi–square tests as appropriate with p < 0.05 considered significant. Data are shown as mean ± SD.ResultsMedetomidine significantly decreased plasma insulin concentrations and increased plasma glucose concentrations in healthy dogs and those with insulinoma. These variables did not change significantly in the dogs not receiving medetomidine. In the dogs with insulinoma, intra–operative glucose administration rate was significantly less in the animals that received medetomidine compared to those that did not.ConclusionsPre–anesthetic administration of medetomidine significantly suppressed insulin secretion and increased plasma glucose concentration in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.Clinical relevanceThese findings support the judicious use of medetomidine at low doses as an adjunct to the anesthetic management of dogs with insulinoma.     

Laboratory diagnosis of insulinoma in the dog: A retrospective study and a new diagnostic procedure

Simultaneous insulin and glucose measurements from a single sample are often insufficient for the laboratory diagnosis of insulinoma in the hypoglycaemic dog. Although the simple insulin ((xU/litre): glucose (mmol/litre) ratio is best, when the selected threshold is set at 13-5, it is not always efficient to confirm or refute insulinoma. The fasting test consists of collecting four samples on a given day (no accurate time period is set between any two samples) from a fasting dog for simultaneous insulin and glucose measurements to detect at least one abnormal insulinaemia peak.     

Investigation of the effect of acepromazine on intravenous glucose tolerance tests in dogs

OBJECTIVE: To investigate the effects of administration of acepromazine on IV glucose tolerance tests (IVGTTs) in dogs. ANIMALS: 8 male mixed-breed dogs. PROCEDURE: With a 1-week interval between tests, each dog underwent (in random order) an IVGTT with or without pretest administration of acepromazine maleate (0.1 mg/kg, SC, 30 minutes prior to the start of the IVGTT). Food was withheld from the dogs for 14 hours prior to each test. Blood samples were obtained at 20, 10, and 1 minute prior to and at 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180 minutes after administration of glucose. RESULTS: There were no significant differences in the baseline (ie, after food was withheld) plasma glucose, lactate, and insulin concentrations between dogs undergoing the IVGTT and acepromazine-IVGTT; however, lower baseline free fatty acid concentration was observed in acepromazine-treated dogs. Analysis of data via the application of Bergman's minimal model of glucose kinetics revealed no differences in insulin sensitivity, acute insulin response to glucose, disposition index, or glucose effectiveness between dogs treated or not treated with acepromazine before testing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that in dogs undergoing IV glucose tolerance testing, pretest administration of small doses of acepromazine can be used as a means of chemical restraint without interfering with results of the glucose metabolism assessment.     

Insulinoma in a ferret

Insulinoma was diagnosed in a 7-year-old female ferret examined because of generalized seizures, intermittent paraplegia, and abnormal behavior. Low serum glucose, high serum insulin, and infinite amended insulin/glucose ratio values in this ferret supported the clinical diagnosis of insulinoma. Histologic examination of the pancreas confirmed the diagnosis of insulinoma. The clinical signs and laboratory evaluations in this case and in a previously reported case of insulinoma in a ferret were consistent with variations reported in dogs with insulinoma.     

Clinical significance of plasma mannose concentrations in healthy and diabetic dogs

Circulating levels of monosaccharides can act as a reflection of systemic glucose/ energy metabolism. Characteristic changes observed in these levels can be seen in patients with diabetes and other metabolic disorders. There have been a few reports describing the significance of mannose metabolism as an energy source under physiological and pathological conditions. However, the relationship between circulating levels of mannose and the pathophysiology of diabetes mellitus are unknown in dogs. This study examined circulating levels of mannose between healthy control and diabetic dogs and evaluated the clinical significance of mannose levels in dogs. Diabetic dogs demonstrated a higher circulating level of mannose in comparison to normal healthy control dogs. Plasma mannose was positively correlated with plasma glucose and fructosamine, respectively. Interestingly, plasma mannose levels were affected by plasma insulin levels. In the context of feeding and glucose tolerance tests, plasma mannose levels responded to changes in circulating insulin levels. Circulating plasma mannose levels decreased after feeding in both control and diabetic animals in spite of observed insulin level differences. However, when glucose tolerance tests were given, a positive correlation between mannose levels and insulin levels was observed. Therefore, plasma mannose levels obtained via glucose tolerance testing may be used as a new diagnostic method for evaluating insulin resistance or deficiency in diabetic dogs.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

The effect of ciclosporin A (CsA) on glucose homeostasis was investigated in 16 dogs with atopic dermatitis by determining plasma glucose, serum fructosamine and insulin concentrations, and serial insulin and glucose concentrations following a glucagon stimulation test, before and 6 weeks after CsA therapy at 5 mg/kg once daily. All dogs completed the study. Following CsA treatment, the median serum fructosamine concentrations were significantly higher (pretreatment 227.5 μmol/L; post-treatment 246.5 μmol/L; P = 0.001; reference range 162-310 μmol/L). Based on analyses of the areas under concentration-time curves (AUC) pre- and post-CsA treatment, plasma glucose concentrations were significantly higher (AUC without baseline correction 31.0 mmol/L/min greater; P = 0.021) and serum insulin concentrations were significantly lower (AUC without baseline correction 217.1 μIU/mL/min lower; P = 0.044) following CsA treatment. Peak glucose concentrations after glucagon stimulation test were significantly higher following CsA treatment (10.75 versus 12.05 mmol/L; P = 0.021), but there was no significant difference in peak serum insulin (52.0 versus 35.0 μIU/mL; P = 0.052). There was a negative correlation between baseline uncorrected insulin AUC and trough serum log CsA concentrations (r = -0.70, P = 0.005). The administration of CsA to dogs with atopic dermatitis leads to disturbances in glucose homeostasis. The clinical significance of this is unclear, but it should be taken into account when considering CsA treatment in dogs that already have such impairments.     

Blood glycated hemoglobin evaluation in sick dogs.

Blood glycated hemoglobin concentration reflects long-term serum glucose levels in dogs. In this study, the effects of several diseases on blood glycated hemoglobin levels have been evaluated. For this study, blood samples were drawn from 93 unhealthy dogs. The animals were distributed into 10 groups according to pathological process (group 1, digestive problems; group 2, leishmaniasis; group 3, anemia; group 4, dermatological disorders; group 5, urinary problems; group 6, cardiorespiratory problems; group 7, diabetes mellitus; group 8, insulinoma; group 9, general diseases; group 10, control group). Blood glucose and glycated hemoglobin concentrations and hemoglobin and hematocrit values were analyzed in all the animals. In diabetic dogs, a strong increase in blood glycated hemoglobin was observed when compared with the other groups (P < 0.01). In contrast, dogs with insulinoma showed a decrease in blood glycated hemoglobin, though significant differences were not reported in all cases. No change in blood glycated hemoglobin concentrations were reported in dogs affected by other diseases. So, we can suppose that only the chronic alterations in glucose metabolism (chronic hyper- or hypoglycemia) can induce significant changes on the blood glycated hemoglobin concentrations in dogs.     

CONTRAST‐ENHANCED ULTRASONOGRAPHIC FINDINGS IN THREE DOGS WITH PANCREATIC INSULINOMA

Abdominal ultrasonography is one of the most common diagnostic imaging modalities used for dogs with suspected insulinoma; however, pancreatic masses are clearly identified in fewer than half of affected dogs and benign pancreatic nodules can be difficult to differentiate from malignant ones. The purpose of this prospective study was to describe contrast‐enhanced ultrasonography (CEUS) characteristics of confirmed pancreatic insulinoma in a group of dogs. Inclusion criteria were as follows: (1) repeated hypoglycemia (blood glucose levels <60 mg/dl, twice or more); (2) elevated blood insulin levels with hypoglycemia; (3) pancreatic nodules detected with conventional ultrasonography; and (4) histological confirmation of pancreatic islet cell carcinoma. Immediately following conventional ultrasonography of the entire abdomen, CEUS of the pancreatic nodule and adjacent parenchyma was performed using contrast‐specific technology pulse inversion imaging and perflubutane microbubble contrast agent. Three dogs met inclusion criteria. Pancreatic nodules in all the three dogs became more clearly demarcated after injection of the contrast agent. Each nodule showed different enhancement patterns: markedly hyperechoic for 5 s, slightly hyperechoic for 1 s, and clearly hypoechoic for over 30 s. These results were not in complete agreement with previously reported CEUS findings in human patients with insulinoma. All nodules were surgically resected and histopathologically confirmed as malignant insulinomas. Findings from the current study indicated that contrast‐enhanced ultrasound may help to increase conspicuity of pancreatic insulinomas in dogs and that enhancement characteristics may be more variable in dogs than in humans.     

High-fat feeding and staphylococcus intermedius infection impair beta cell function and insulin sensitivity in mongrel dogs

As obesity is a state of low-grade inflammation, we aimed to investigate the combined effect of high-fat diet and bacterial infection on β-cell function and insulin sensitivity in dogs. We used 20 healthy, male, mongrel dogs randomly divided into four groups: control group—healthy, non-obese dogs; infected group—non-obese dogs with experimentally induced infection (Staphylococcus intermedius); obese group—obese dogs (after 90 day high-fat diet) and obese-infected group—obese dogs with experimentally induced infection (Staphylococcus intermedius). To evaluate insulin sensitivity and β-cell function an intravenous glucose tolerance test (IVGTT) was performed. Plasma insulin increased in all group after glucose infusion. The lowest values were found in obese-infected group. Blood glucose also increased on 3 min after glucose infusion and then gradually decreased. In obese-infected group glucose concentration on 30 min was still significantly higher than initial levels, while in other groups glucose concentration returned to the initial values. The lowest rate of glucose elimination was found in infected group. In dogs of obese group and obese-infected group AUC_{ins 0–60 min} was lower compared to controls. AUC_{glucose 0–60 min} values were lowest in infected group, while in obese-infectd group values were the highest. Levels of ∆I/∆G in dogs of obese-infected group were significantly lower compared to controls and infected group. In conclusion, these results reveal that infection in obese dogs leads to impaired glucose tolerance, which is result of impairment in both insulin secretion and insulin sensitivity.     

Effect of Weight Gain and Subsequent Weight Loss on Glucose Tolerance and Insulin Response in Healthy Cats

The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre-study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat. Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P > .05) increased after weight gain, as compared with baseline. At the end of weight loss, cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P > .05) increase in mean serum glucose concentration and t_1/2, and a significant (P > .05) decrease in mean serum insulin concentration and the glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulino-genic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P > .05), compared with measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P > .05) in measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the number and size of lipid vacuoles in hepatocytes had decreased, and results of IVGTT were similar to those obtained at baseline. These findings confirmed the reversibility of obesity-induced insulin resistance in cats, and documented initial deterioration in glucose tolerance and insulin response to glucose infusion when weight loss was caused by severe restriction of caloric intake.     

Evaluation of the long-acting somatostatin analogue Octreotide in the management of insulinoma in three dogs

The response of dogs with insulinoma to surgical and medical management is variable, with the majority developing intractable hypoglycaemia. A long-acting somatostatin analogue, Octreotide (SMS 201–995; Sandostatin) has been useful in the management of hypoglycaemia in humans with insulinoma, and preliminary reports suggest a beneficial clinical response in dogs with insulinoma. The present study objectively evaluated Octreotide in the management of three dogs with immunohistochemically confirmed insulinoma. Octreotide had no benefit over placebo, and little effect on circulating glucose and insulin concentrations despite clearly detectable plasma concentrations of Octreotide. No clinical improvement was apparent in two dogs given Octreotide over a period of two and three weeks. These results contrast with the positive clinical responses noted previously and indicate that further placebo controlled, objective studies are necessary before clear statements on the treatment of insulinoma with Octreotide are made.     

Mega-oesophagus secondary to acquired myasthenia gravis

Fifteen dogs with confirmed adult onset idiopathic megaoesophagus, in which no generalised muscle weakness was observed, were tested for the presence of acetylcholine receptor antibodies. Of these, six were found to have values greater than 0–6 nmol/litre, previously determined to be diagnostic of acquired myasthenia gravis. The mean serum titre value for these dogs was 5–59 nmol/litre (range 0–78 to 8–72 nmol/litre). It appears that a significant proportion of dogs presenting with megaoesophagus have myasthenia gravis and, if a prompt diagnosis and appropriate treatment can be instituted, clinical signs may improve.     

Malate dehydrogenase activities are lower in some types of peripheral leucocytes of dogs and cats with type 1 diabetes mellitus

The activities of the enzymes in the malate-aspartate shuttle were measured in peripheral leucocytes of spontaneous type 1 diabetic dogs and cats treated with insulin injections. In the diabetic dogs and cats, fasting plasma glucose concentrations were three- or fourfold greater than the control levels in spite of insulin injections and the activities of cytosolic malate dehydrogenase (MDH), one of pivotal enzymes in the malate-aspartate shuttle, were remarkably lower than the controls. Depressed expression of cytosolic MDH mRNA was confirmed by RT-PCR analysis in the diabetic animals. The cytosolic ratio of MDH/lactate dehydrogenase (LDH) activity (M / L ratio) in leucocytes of the diabetic animals was significantly lower than that of normal control animals. The smaller M / L ratio appeared to reflect depression of energy metabolism in the diabetic animals. Intrinsically lower and further decreased MDH activities may be factors that induce insulin resistance observed in diabetic cats.     

Idiopathic hyperchylomicronaemia in miniature schnauzers

Several authors have reported the presence of fasting hyperlipidaemia in adult miniature schnauzers presented with either paroxysmal abdominal pain, vomiting or diarrhoea. Acute pancreatitis is commonly confirmed. There appears to be no sex predilection for the condition although the majority of affected dogs are middle aged and older. Lipid profiles of affected dogs reveal extreme elevations of fasting serum triglyceride (TG) concentrations ranging from 5·5 mmol/litre to over 90 mmol/litre; the hyperlipidaemia is almost exclusively attributed to chylomicron excess. To date, the reviewer's studies have not shown a correlation between TG levels and severity of signs. However, miniature schnauzers with fasting TG levels greater than 5·5 mmol/litre are considered to be at significant risk and should be further evaluated as candidates for dietary intervention.     

Glucose tolerance and insulin response in diabetes mellitus of dogs

The low dose intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose load were performed in a series of twenty–two diabetic dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half time (Tl/2) or fractional turnover rate (k) for glucose clearance. On the basis of the initial insulin level (Io), the insulin peak response (Ip) and the insulinogenic index (I/G), the dogs were classified into three types. Type I dogs were characterized by a low Io, low Ip and low I/G in response to glucose, similar to the juvenile form of diabetes in humans. Type II dogs were characterized by a normal or high Io, but also with a low Ip and a low I/G which are some of the features of the maturity onset form. Type III dogs were characterized by a normal Io and a normal or delayed response to glucose as seen in chemical diabetes. It is suggested that these types represent stages in the natural history of the development of diabetes mellitus in dogs.