This is the first of approximately six articles reviewing presentations at this meeting. Mark Burge, Albuquerque, New Mexico, introduced the topic of diabetic gastroparesis. The role of the stomach is to mix, pulverize, and deliver food to the duodenum.
Gastric motor activity is controlled by many factors, including extrinsic parasympathetic and sympathetic and intrinsic enteric nerves and hormones such as gastrin, motilin, glucagon-like peptide-1, neuropeptide-Y, and nitric oxide. The glucagon-like peptide-1 agonist NN delays gastric emptying in people with diabetes and may be beneficial for the overly rapid gastric emptying, which appears to worsen postprandial glycemia, of many individuals with type 1 diabetes.
Gastric peristalsis is controlled by electrical impulses originating from gastric pacemaker cells, depolarizing three times per minute, with the fundus exhibiting receptive relaxation, while the antrum has regular contractions leading to vigorous mixing and grinding. Gastroparesis is potentiated by a number of factors, including gastric dysrhythmia, discoordination of antral contractions, failure of the fundus to relax, and hypomotility or inappropriate dilation antibacterial personal catheters the antrum.
Nausea, particularly following meals, vomiting, abdominal pain, bloating with malodorous eructation, early satiety, and anorexia are usual symptoms, although not typically with weight loss, which may indicate an eating disorder or additional gastrointestinal illness.
There is poor relationship between the severity of gastropathy american diabetes association annual meeting the symptoms exhibited by a given person. As symptoms alone are insufficient, it is important to objectively assess gastric function. Measurement of gastric emptying should be performed if possible when the patient is euglycemic, or if this is not possible, it is important to record the glucose level during the american diabetes association annual meeting. The scintigraphic assessment of gastric emptying of a technetium-labeled meal is most commonly performed, reporting the half-time for gastric emptying.
For adequate assessment, 4-h gastric emptying studies are required, rather than using shorter studies and then extrapolating. Related tests include sonographic measurement of gastric emptying, acetaminophen absorption, electrogastrography, and intraluminal pressure measurement.
Gastroscopy or other evaluation may be required to exclude structural abnormality in selected individuals. Richard McCallum, Kansas City, Kansas, noted that the three-cycles-per-minute electrical rhythm of the antrum usually is not associated with a contractile response, but that after vagal stimulation signals such as motilin are released, the electrical signal causes gastric smooth muscle contraction.
Physiologically, the interstitial cells of Cajal are spontaneously depolarizing gastric pacemaker cells that lead to contraction if excitatory signals are being conveyed in the gastric myenteric plexus. Hyperglycemia tacchygastria develops in approximately one-third of patients and may be prostaglandin-mediated, and there is some evidence of a response to indomethacin, suggesting a role of prostaglandin synthesis inhibitors in treatment.
McCallum noted that sildenafil relaxes the antrum and, therefore, would not be expected to be effective for gastroparesis, despite the potential role of nitric oxide-induced cGMP production. Interestingly, the agent has been successfully used for esophageal motility disorders such as achalasia, american diabetes association annual meeting.
Treatment for patients failing to respond to pharmacologic agents included surgical placement of jejeunostomy for maintaining nutrition and the use of gastric pacing. Two approaches have been used: American diabetes association annual meeting device is implanted by laparotomy or laparoscopy with two electrodes proximal to the pylorus. McCallum has now treated a total of 38 subjects with diabetes and gastroparesis who had previously had numerous hospitalizations for this condition.
After 1 year, hospitalization rates are very low. McCallum speculated that the device leads to return of function of the interstitial cells of Cajal. Antral biopsy of these patients has shown, however, that interstitial cells of Cajal are absent in approximately one-third of cases; therefore, some patients will fail to respond to the low-energy stimulator. These patients may need direct stimulation of muscle with higher-energy impulses. Although gastrojejeunostomy has occasionally been performed with the rationale of decompressing the dilated stomach and allowing feeding, he suggested that this approach often leads to severe fluid and electrolyte disturbance and should be avoided.
Some patients require total gastrectomy with esophageal-jejeunal anastomosis, but this extreme approach must be reserved for those who fail to respond to all other approaches. McCallum presented three cases illustrating other aspects of treatment. The first was of a year-old woman who had had diabetes for 25 years and a lb weight loss that was regained with total parenteral nutrition.
At 6-month follow-up, she was improving. She planned to obtain domperidone from New Zealand it is less expensive there than in Canada to enhance gastric emptying and to try metronidazol for presumed bacterial overgrowth.
The second patient was a year-old female with a year diabetes history and a 1-year history of gastroparesis who experienced severe nausea and vomiting 10 times a day at 3- to 4-day intervals. Treatment is with cisapride no longer commercially available because of the potential for ventricular arrhythmia and hence requiring electrocardiographic monitoringdomperidone, erythromycin acting as a motilin agonistand low-fat, low-fiber, small, frequent feedings with the use of a backup nutrient liquid such as Ensure at night.
McCallum suggested the use of transdermal scopolamine, as nausea is an important symptom requiring ongoing prophylactic treatment. The phenothiazine derivative promethazine may also be american diabetes association annual meeting for nausea, although, like scopolamine, its anticholinergic effect may lead to a small further decrease in gastric emptying.
Tegaserod, a serotoninergic agonist developed for irritable bowel syndrome, promotes upper gut motility and may play a role.
New motilin agonists such as GM Chugai Pharmaceuticals are being developed and may prove useful. Bacterial overgrowth is common and should be treated with metronidazole, amoxicillin-clavulinic acid, neomycin, or probiotics such as acidophilus-containing products.
Clonidine treatment may be effective, always starting with a low dosage to avoid hypotension. Patients with diabetes and severe diarrhea should have evaluation to exclude other gastrointestinal illness such as celiac disease. The final case was of a year-old woman with an month history of gastrointestinal symptoms, treated with 10 mg metoclopramide s.
McCallum suggested that this is an important agent, acting both via cholingergic and antidopaminergic pathways to enhance gastric emptying, and should particularly be given in the morning when nausea is most severe, as the patient must not begin vomiting, which can lead to uncontrolled diabetes and a cycle of worsening requiring hospitalization.
In this case, a gastrostomy had been placed for continuous drainage and a jejeunostomy for feeding, the former causing severe potassium deficiency. He treated her pain with transcutaneous fentanyl, although methadone may be better than other opiates because of fewer gastrointestinal and neurologic side effects. Marion Franz, Mineapolis, Minnesota, introduced a symposium on the role of protein in diabetes, american diabetes association annual meeting, addressing issues of nutrition and metabolism.
There is a great deal of research on one of the macronutrients, carbohydrate, but evidence is relatively limited addressing the roles of protein. Over the past 90 years, protein intake has been remarkably consistent in the U.
Protein digestion begins in the stomach, is continued by pancreatic proteinases, with subsequent protein breakdown into di- and tripeptides and then american diabetes association annual meeting as amino acids across the intestinal mucosa, entering the portal vein, although glutamine, american diabetes association annual meeting, glutamate, and aspartate are used in part for fuel by gut mucosal cells. None of this glucose, however, american diabetes association annual meeting, appears in the general circulation, perhaps because the protein was slowly digested, the glucose was stored as glycogen in the liver, or the amount converted into glucose had not been accurately calculated.
The effect of protein depends on the availability of insulin and on glycemic control. Adequate insulin is required for control of american diabetes association annual meeting catabolism and gluconeogenesis. Franz summarized the latest ADA recommendations pertaining to dietary protein. For individuals with controlled type 2 diabetes, and perhaps for those with type 1 diabetes, protein ingestion does not increase plasma glucose concentrations.
With less than adequate glycemic control, protein requirements may exceed the recommended dietary allowance, although not exceeding usual dietary intake levels. For people with nephropathy, although there is somewhat less evidence, protein intake should be reduced to 0. If renal function is normal, there is no evidence as to the benefits of changing dietary protein intake. The long-term effects of diets high in protein and low in carbohydrates are unknown, although it appears that such diets do lead to weight loss and improvement in glycemia, although not necessarily to a greater extent than that with other diets.
There is no evidence that protein slows carbohydrate absorption or that adding protein to food ingested for hypoglycemia or ingesting protein-containing foods at bedtime is helpful for the prevention of subsequent hypoglycemia, although these measures have typically been recommended for subjects with type 1 diabetes. Errol Marliss, Montreal, Canada, discussed the implications of altered protein turnover in diabetes.
Glucose production, related to the fall in insulin with rise or lack of change in glucagon, leading to gluconeogenesis, is accelerated under conditions of insulin deficiency. With exogenous amino acids and glucose, as seen american diabetes association annual meeting a meal, glucose production increases further in the insulin-deficient patient.
There is not, however, evidence of abnormal protein metabolism in treated subjects with diabetes. This may be due to the focus on the fasted state of most existing research.
Worse degrees of glycemic control are associated with various degrees of protein catabolism. Oral hypoglycemic agents and exogenous insulin increase protein synthesis and decrease protein catabolism.
In studies of obese individuals, a low-energy high-protein diet tends to be associated with similar degrees of protein balance with and without diabetes. Marliss concluded that with hyperglycemia, american diabetes association annual meeting, dietary protein requirements may increase, and he recommended that individuals with diabetes avoid very-low-protein diets. Mary Gannon, Minneapolis, Minnesota, reviewed the effects of dietary protein on circulating insulin and glucose concentrations.
The amino acids that result from protein digestion have long been known to be available for gluconeogenesis, with 56 g glucose theoretically available to be produced for every g meat protein ingested and the glucose-generating capacity of g of various proteins ranging from 50 to 80 g. Glucose concentrations do not, however, change after ingestion of protein. This appears to be mainly due to the increase in insulin after protein ingestion.
Gannon noted that when 50 g protein was given to control and type 2 su and diabetes subjects, there was no increase and a small decrease in glucose, respectively, in association with an increase in insulin levels, which occurred to a greater extent in people with diabetes.
Studying a variety of protein sources given with dietary carbohydrate, cottage cheese, beef, turkey, gelatin, egg white, fish, and soy all stimulate insulin secretion to varying degrees. Julie Eisenstein, Boston, Massachusetts, reviewed the relationship between dietary protein and weight loss. Although, she noted, epidemiologic studies suggest a positive correlation between dietary protein and weight gain, the popular conception is that dietary protein can be helpful in causing weight loss, american diabetes association annual meeting.
Although the RDA is 0. There are a limited number of studies in this area of nutrition, and it is noteworthy that a high-protein calorie-restricted diet may actually not be high in protein, but instead may be low in other macronutrients, american diabetes association annual meeting.
In short-term studies, a high-protein meal is associated with decreased subsequent food ingestion, suggesting suppression of hunger. Long-term studies, however, american diabetes association annual meeting, show equivocal evidence of decreased energy intake. An additional factor is that the thermic effect of feeding as a percent of energy intake appears to double after a protein meal compared with a fat or carbohydrate meal, american diabetes association annual meeting.
Furthermore, the decrease in resting energy expenditure after weight loss may be lessened in individuals following a high-protein diet. The first, which compared 25 vs. Eisenstein concluded that in diets of similar calorie content, there is no evidence of benefit, but that with ad libitum diets, there is some evidence of benefit of high-protein approaches, although more data on long-term safety are needed.
Some studies show a relationship between dietary protein and microalbuminuria 4but other studies have not confirmed this relationship 5. Short-term studies have addressed the early phase of renal disease, with one study showing that high 1.
In individuals with macroalbuminuria, there is only equivocal evidence of benefit. As far as the protein source, there is some evidence of benefit of a low-calorie soy protein diet 9but the comparison of low-calorie plant protein with animal plus plant protein has shown no difference in albuminuria or glomerular filtration rate. One study suggested lesser levels of albuminuria with a diet containing protein derived from chicken than one using beef 7.
Elina Hypponen London, U. Vitamin D should be considered a hormone rather than a nutrient, with metabolic actions mediated by receptors. Deficiency causes rickets in children and osteomalacia in adults, while excess causes hypercalcemia, but there is also evidence of an important immunomodulatory role affecting several Th1-type cytokines and dendritic cell maturation that may potentially alter the pathogenic steps leading to type 1 diabetes.
Administration of 1,25 dihydroxy vitamin D decreases progression to diabetes among NOD mice, with evidence of a dose-related effect, although only at doses associated with hypercalcemia. In humans, the EURODIAB study of vitamin D supplementation in infancy appeared to decrease the development of type 1 diabetes 10american diabetes association annual meeting, and there is evidence that cod liver oil intake during pregnancy decreases type 1 diabetes risk For those children regularly receiving vitamin D supplements, there was a dose effect, with higher doses further decreasing risk.
Children with possible rickets during the first years of life had a particularly high risk of american diabetes association annual meeting 1 diabetes. Hypponen pointed out, however, that vitamin D supplementation recommendations have been decreased and that this may be a factor in the recent increase in type 1 diabetes frequency.