RESUMO
OBJECTIVE: As part of our studies of the metabolic effects of ingested proteins, we are currently investigating the effects of ingestion of individual amino acids. The objective of the present study was to determine whether ingested phenylalanine stimulates insulin and/or glucagon secretion, and if phenylalanine ingested with glucose modifies the insulin, glucagon or glucose response to the ingested glucose. DESIGN: Six healthy subjects were tested on 4 separate occasions. Plasma phenylalanine, glucose, insulin, glucagon, and total alpha amino nitrogen (AAN) (i.e., total amino acids) concentrations were measured at various times during a 2.5 h period after ingestion of 1 mmol phenylalanine/kg lean body mass, 25 g glucose, 1 mmol phenylalanine/kg lean body mass+25 g glucose, or water only, given in random order. RESULTS: Following phenylalanine ingestion, the circulating phenylalanine concentration increased approximately 14 fold and remained elevated for the duration of the experiment. Glucagon and AAN increased, insulin increased modestly, and glucose was unchanged when compared to water ingestion. When glucose was ingested with phenylalanine, the circulating phenylalanine, glucagon, AAN, and insulin area responses were approximately the sum of the responses to phenylalanine alone and glucose alone. However, the plasma glucose area response was decreased 66% when phenylalanine was co-ingested with glucose. CONCLUSION: In summary, phenylalanine in an amount moderately greater than that in a large protein meal stimulates an increase in insulin and glucagon concentration. It markedly attenuates the glucose-induced rise in plasma glucose when ingested with glucose.
Assuntos
Glicemia/metabolismo , Glucagon/sangue , Glucose/administração & dosagem , Insulina/sangue , Fenilalanina/administração & dosagem , Edulcorantes/administração & dosagem , Administração Oral , Adulto , Combinação de Medicamentos , Feminino , Humanos , MasculinoRESUMO
Amino acids derived from ingested protein are potential substrates for gluconeogenesis. However, several laboratories have reported that protein ingestion does not result in an increase in the circulating glucose concentration in people with or without type 2 diabetes. The reason for this has remained unclear. In people without diabetes it seems to be due to less glucose being produced and entering the circulation than the calculated theoretical amount. Therefore, we were interested in determining whether this also was the case in people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes were given, in random sequence, 50 g protein in the form of very lean beef or only water at 0800 h and studied over the subsequent 8 h. Protein ingestion resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids; and a modest increase in respiratory quotient. The total amount of protein deaminated and the amino groups incorporated into urea was calculated to be approximately 20-23 g. The net amount of glucose estimated to be produced, based on the quantity of amino acids deaminated, was approximately 11-13 g. However, the amount of glucose appearing in the circulation was only approximately 2 g. The peripheral plasma glucose concentration decreased by approximately 1 mM after ingestion of either protein or water, confirming that ingested protein does not result in a net increase in glucose concentration, and results in only a modest increase in the rate of glucose disappearance.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Proteínas Alimentares/administração & dosagem , Adulto , Idoso , Animais , Peptídeo C/sangue , Bovinos , Ritmo Circadiano , Ingestão de Líquidos , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Carne , Pessoa de Meia-Idade , Triglicerídeos/sangue , Ácido Úrico/sangueRESUMO
Galactose is one of the monosaccharides of importance in human nutrition. It is converted to glucose-1-phosphate in the liver and subsequently stored as glycogen, or is converted to glucose and released into the circulation. The increase in plasma glucose is known to be modest following galactose ingestion. Whether this is due to a small increase in hepatic glucose output, or to a relatively large increase in hepatic glucose output but a concomitant increase in glucose disposal, is not known in humans. Therefore, the rates of glucose appearance (Ra) and disappearance (Rd) were determined over an 8-hour period in normal subjects using an isotope dilution technique. The subjects ingested 50 g galactose or water alone in random order at 8 AM on separate occasions. Plasma glucose, glucagon, lactate, urea nitrogen, total amino acids, and uric acid and serum insulin and triglycerides also were determined. Following galactose ingestion, there was a modest transient increase in peripheral glucose and insulin concentrations. This was associated with a modest increase in the glucose Ra. The calculated amount of glucose appearing in the circulation as a result of galactose ingestion was 9.8 g, while the amount of glucose disappearing over the 8 hours was 9.9 g. Thus, following ingestion of 50 g galactose by overnight-fasted men, approximately 20% appears as additional glucose in the circulation. Data obtained in animals suggest that a large amount of the galactose is stored as glucose in glycogen. Nevertheless, the conversion of galactose to glucose in the liver may have been greater than suggested by the increase in glucose appearance in the circulation due to substitution for other gluconeogenic substrates.
Assuntos
Galactose/farmacologia , Glucose/biossíntese , Adulto , Glicemia/análise , Galactose/metabolismo , Humanos , Masculino , Ureia/sangue , Ácido Úrico/sangueRESUMO
We have reported that glycogen synthesis and degradation can occur in vivo without a significant change in the amount of phosphorylase a present. These data suggest the presence of a regulatable mechanism for inhibiting phosphorylase a activity in vivo. Several effectors have been described. AMP stimulates, whereas ADP, ATP, and glucose inhibit activity. Of these effectors, only the glucose concentration changes under normal conditions; thus it could regulate phosphorylase a activity in vivo. We previously have reported that, when all of these effectors were present at physiological concentrations, the net effect was no change in phosphorylase a activity. Addition of caffeine, an independent inhibitor of activity, to the above effectors not only resulted in inhibition but also restored a glucose concentration-dependent inhibition. Because uric acid is an endogenous xanthine derivative, we decided to determine whether it had an effect on phosphorylase a activity. Independently, uric acid did not affect activity; however, when added at a presumed physiological concentration in combination with AMP, ADP, ATP, and glucose, it inhibited activity. A modest but not statistically significant glucose concentration-dependent inhibition was also present. Thus uric acid may play an important role in regulating phosphorylase a activity in vivo.
Assuntos
Inibidores Enzimáticos/farmacologia , Fígado/enzimologia , Fosforilase a/antagonistas & inibidores , Ácido Úrico/farmacologia , Nucleotídeos de Adenina/farmacologia , Animais , Cafeína/farmacologia , Combinação de Medicamentos , Glucose/metabolismo , Glucose/farmacologia , Masculino , Concentração Osmolar , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Microalbuminuria can reflect the progress of microvascular complications and may be predictive of macrovascular disease in type 2 diabetes. The effect of intensive glycemic control on microalbuminuria in patients in the U.S. who have had type 2 diabetes for several years has not previously been evaluated. RESEARCH DESIGN AND METHODS: We randomly assigned 153 male patients to either intensive treatment (INT) (goal HbA(1c) 7.1%) or to standard treatment (ST) (goal HbA(1c) 9.1%; P = 0.001), and data were obtained during a 2-year period. Mean duration of known diabetes was 8 years, mean age of the patients was 60 years, and patients were well matched at baseline. We obtained 3-h urine samples for each patient at baseline and annually and defined microalbuminuria as an albumin:creatinine ratio of 0.03-0.30. All patients were treated with insulin and received instructions regarding diet and exercise. Hypertension and dyslipidemia were treated with similar goals in each group. RESULTS: A total of 38% of patients had microalbuminuria at entry and were evenly assigned to both treatment groups. INT retarded the progression of microalbuminuria during the 2-year period: the changes in albumin:creatinine ratio from baseline to 2 years of INT versus ST were 0.045 vs. 0.141, respectively (P = 0.046). Retardation of progressive urinary albumin excretion was most pronounced in those patients who entered the study with microalbuminuria and were randomized to INT. Patients entering with microalbuminuria had a deterioration in creatinine clearance at 2 years regardless of the intensity of glycemic control. In the group entering without microalbuminuria, the subgroup receiving ST had a lower percentage of patients with a macrovascular event (17%) than the subgroup receiving INT (36%) (P = 0.03). Use of ACE inhibitors or calcium-channel blockers was similarly distributed among the groups. CONCLUSIONS: Intensive glycemic control retards microalbuminuria in patients who have had type 2 diabetes for several years but may not lessen the progressive deterioration of glomerular function. Increases in macrovascular event rates in the subgroup entering without albuminuria who received INT remain unexplained but could reflect early worsening, as observed with microvascular disease in the Diabetes Control and Complications Trial.
Assuntos
Albuminúria , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/urina , Insulina/uso terapêutico , Adulto , Idoso , Automonitorização da Glicemia , Creatinina/urina , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Exercício Físico , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Abandono do Hábito de Fumar , Fatores de TempoRESUMO
OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) was a multicenter randomized prospective study of 153 male type 2 diabetic patients to assess the ability to sustain clinically significant glycemic separation between intensive and standard treatment arms. A trend toward an excess of combined cardiovascular events in the intensive treatment arm of this trial was reported earlier. The present analysis was done to evaluate the effect of 2 years of intensive glycemic control on the left ventricular (LV) function. RESEARCH DESIGN AND METHODS: The patients were randomized to intensive step treatment with insulin alone or with sulfonylurea (intensive treatment arm [INT], n = 75) or to standard once-daily insulin injection (standard treatment arm [STD], n = 78) treatment. A total of 136 patients (standard treatment arm [STD], n = 70; INT, n = 66) had radionuclide ventriculography at entry and at 24 months for the assessment of LV function. RESULTS: There was no difference in the mean LV ejection fraction (at entry: STD 57.1+/-9.51%; INT 58.1+/-8.7%; at 24 months: STD 57.3+/-10.8%, INT 59.5+/-10.7%), peak filling rate (at entry: STD 2.6+/-0.7 end diastolic volume per second, INT 2.4+/-0.8 end diastolic volume per second; at 24 months: STD 2.7+/-1.0 end diastolic volume per second, INT 2.5+/-0.7 end diastolic volume per second), or time to peak filling rate (at entry: STD 195.3+/-69.5 ms, INT 185.6 +/-62.4 ms; at 24 months: STD 182.6+/-64.8 ms, INT 179.2+/-61.2 ms) between the 2 treatment arms. A subgroup analysis of 104 patients (STD, n = 53; INT, n = 51) that omitted individuals with intervening cardiac events/revascularization or a change in cardioactive medications also showed no difference in the LV function at entry and at 24 months between the 2 groups. Abnormal LV ejection fraction at baseline predicted cardiac events (interval between cardiac beats [RR] = 2.5). CONCLUSIONS: Two years of intensive glycemic control does not affect the LV systolic or diastolic function in patients with type 2 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Hipoglicemiantes/uso terapêutico , Função Ventricular Esquerda , Pressão Sanguínea , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ventriculografia com Radionuclídeos , Compostos de Sulfonilureia/uso terapêutico , Fatores de TempoRESUMO
Paget disease of the bone is a common skeletal disorder. Recently, a gene for Paget disease was localized to 18q with subsequent evidence for linkage heterogeneity. We report the identification and clinical characterization of a large pedigree of Paget disease and demonstrate that the Paget disease gene in this pedigree is not linked to the region on 18q, thus confirming linkage heterogeneity.
Assuntos
Heterogeneidade Genética , Osteíte Deformante/genética , Adulto , Idoso , Cromossomos Humanos Par 18 , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Ingested fructose is rapidly utilized by the liver and is either stored as glycogen, converted to glucose, or oxidized to CO2 for energy. The glycemic response to fructose is known to be modest. However, the relative importance of these pathways in humans is unclear. In the present study, a tritiated glucose tracer dilution technique was used to determine the effect of fructose ingestion on the glucose appearance rate (Ra) in the peripheral circulation over an 8-hour period beginning at 8:00 AM. Six normal healthy males ingested 50 g fructose with 500 mL water. On a separate occasion, the same subjects received 500 mL water without fructose as a control. Serum insulin, triglycerides, plasma glucagon, glucose, lactate, alanine, urea nitrogen, and total amino acids also were determined. The plasma glucose concentration was not significantly different following ingestion of fructose or water, other than a transient increase beginning at 8:30 AM of 0.8 mmol/L in response to ingested fructose. Glucose appearing in the peripheral circulation as a result of ingestion of 50 g fructose was calculated to be 9.8 +/- 2.4 g. Following the ingestion of fructose, there was a small increase in glucagon but a 2-fold increase in insulin concentration. There was a large transient increase in lactate and alanine concentrations. The total amino acid concentration remained unchanged, as did the urea production rate. In summary, in men fasted overnight, ingestion of 50 g fructose resulted in a modest increase in the circulating glucose concentration. However, it is likely that a larger proportion of the ingested fructose was converted to glucose in the liver and stored as glycogen and that fructose substituted, at least in part, for lactate and alanine as a gluconeogenic substrate. The increase in glucose production occurred even in the presence of an increase in the insulin concentration and an unchanged glucagon concentration. The metabolic fate of the remaining fructose is yet to be determined.
Assuntos
Glicemia/análise , Frutose/administração & dosagem , Administração Oral , Adulto , Alanina/sangue , Aminoácidos/sangue , Ingestão de Líquidos/fisiologia , Ácidos Graxos não Esterificados/sangue , Frutose/farmacologia , Glucagon/sangue , Humanos , Insulina/sangue , Ácido Láctico/sangue , Masculino , Valores de Referência , Fatores de TempoRESUMO
The purpose of this study was to determine the correlation between age and the percentage of total glycohemoglobin (%tGHb) and that of hemoglobin Alc (%HbA1c) in an adult population without known diabetes. The %tGHb was determined by a semi-automated gravity elution method and by an automated high-performance liquid chromatography (HPLC) method in 210 and 147 subjects without known diabetes, respectively. The %HbA1c, was determined by ion-exchange HPLC in 109 subjects without known diabetes. There was a modest age-related increase in %tGHb and %HbA1c. The mean increase was approximately 0.11% to 0.15% per decade depending on the analytic method used. However, the variance was very large. In conclusion, there is an age-related increase in %tGHb and %HbA1c. However, the increase is only modest and has only a minor effect on a determined reference range in adults.
Assuntos
Envelhecimento/sangue , Hemoglobinas Glicadas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus/sangue , Humanos , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Autoimmune hypoglycemia is a rare but fascinating syndrome of hypoglycemia caused by the interaction of endogenous antibodies with insulin or the insulin receptor. Awareness of autoimmune hypoglycemia is important because the syndrome may produce severe neuroglycopenic symptoms and may be confused with the presence of an insulinoma. A correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy.
Assuntos
Doenças Autoimunes , Hipoglicemia/imunologia , Insulina/imunologia , Receptor de Insulina/imunologia , Anticorpos/sangue , Humanos , Hipoglicemia/diagnósticoRESUMO
OBJECTIVE: Individuals with hyperthyroidism lose weight despite increased appetite and food intake, and weight is regained after treatment of hyperthyroidism. We asked whether this weight regain is purely a function of lowered metabolic rate coincident with lowered thyroid hormone concentrations or if the weight gain is related to food-energy overconsumption. METHODS: Ten unselected patients with hyperthyroidism treated with 131I were studied. The following measurements were made at 0, 1, 2, 3, 6, and 12 months: total food energy, carbohydrate, fat and protein consumption; serum thyroxine (T4); serum triiodothyronine (T3); T3 resin uptake; serum thyroid stimulating hormone (TSH); weight; height; and 24-hour urinary urea excretion. RESULTS: Inverse changes in body weight and food energy consumption/kg throughout the period of observation was a striking finding (mean initial weight 67.1+/-5 kg, final weight 76.4 kg+/-3 kg, premorbid weight 77.1+/-5 kg). The initial and final food energy intake was 3005+/-199 and 2597+/-137 Kcal/24 hrs, respectively. The thyroid hormone concentrations declined inversely relative to weight gain during the first months of the study, but later the thyroid hormones increased while weight gain continued. Initial serum T4 15.0+/-1 value at three months was 4.0+/-1.0 mg/dl, final T4 11.0+/-1. CONCLUSION: We conclude that weight gain following treatment of hyperthyroidism is due to 1) reduction in metabolic rate consequent upon the decreased thyroid hormone concentrations and 2) food energy intake which was initially greater than required to maintain individuals' premorbid weight. As body weight increased, food intake declined and both reached an asymptotic limit.
Assuntos
Ingestão de Energia , Hipertireoidismo/radioterapia , Glândula Tireoide/fisiopatologia , Aumento de Peso , Adulto , Idoso , Estatura , Dieta , Humanos , Hipertireoidismo/fisiopatologia , Radioisótopos do Iodo/uso terapêutico , Pessoa de Meia-Idade , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Ureia/urinaRESUMO
Familial lipodystrophy is a genetically heterogeneous set of disorders characterized by a total or partial absence of subcutaneous fat, diabetes mellitus or impaired glucose tolerance, hyperlipidemia, and hypermetabolism [Senior and Gellis, 1964]. One subtype, familial partial lipodystrophy Dunnigan (FPLD), is a rare autosomal dominant trait that results in an gradual loss of subcutaneous fat in the lower trunk and limbs, Type V hyperlipoproteinemia, hypertriglyceridemia, and insulin-resistant diabetes. Previous reports of this condition have been limited to case reports or very small families. Recently, Peters et al. reported on linkage of five families of Western European descent to a 5.3 cM region on chromosome 1q21-22 between the flanking markers D1S305 and D1S1600 [Peters et al., 1998: Nat Genet 18:292-295]. We performed linkage and haplotype analysis using highly polymorphic, microsatellite markers on a large, multigeneration Caucasian kindred of German ancestry. The maximum two-point lod score achieved was 4.96 at theta(max) = 0 for marker D1S2721. Multipoint analysis gave an overall maximum lod score of 6.27 near marker D1S2721. The results of the haplotype analysis support the minimal candidate region as reported by Peters et al.
Assuntos
Cromossomos Humanos Par 1 , Ligação Genética , Lipodistrofia/genética , Adulto , Mapeamento Cromossômico , Feminino , Haplótipos , Humanos , Masculino , LinhagemRESUMO
To determine whether a difference in HbA(1c) could be safely sustained between a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in community practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy.A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening insulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR variation (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c) at or below 7.3% (p = 0. 001 versus STD). Baseline prevalence of peripheral neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence increased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0. 008 versus baseline, but no different than STD). Though INT did not reverse all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT. By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline and no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 73% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating symptoms. Our conclusion was that 2 years of meticulous glycemic control did not decrease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. There was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Hemoglobinas Glicadas/análise , Insulina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Hospitais de Veteranos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
Nutritional recommendations for patients with type 2 diabetes have changed dramatically over the last 60 years. We present a review of the evolution of these recommendations, as well as a comprehensive overview of the current recommendations for specific food components. The general principles of the nutritional management of type 2 diabetes are: (1) Dietary recommendations for patients with diabetes should be similar to those for the general population; (2) Dietary recommendations should be flexible and highly individualized for the patient and his or her family; (3) Table sugar or foods containing sugar do not need to be restricted to a level less than in a typical American diet; (4) Readily digestible starches raise the blood glucose more than sugars; (5) The effects of weight loss on glycemic control will occur within 2 or 3 months, after which more definitive therapies should be instituted; and (6) Patients should not be stigmatized for failing to lose weight, and weight cycling should be discouraged. Nutritional interventions should concentrate on reducing known risk factors for cardiovascular disease and maintaining glycemic control without jeopardizing the quality of life, the health, or the safety of the patient.
Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos , Fenômenos Fisiológicos da Nutrição , Diabetes Mellitus Tipo 2/fisiopatologia , HumanosRESUMO
The glycogen concentration in liver is altered in various pathophysiologic states. In fasted rats, it is higher in diabetic, and lower in adrenalectomized rats compared to control animals. In fed rats, it is lower in diabetic, and little changed in adrenalectomized animals compared to controls. We were interested in determining whether the activity of glycogenin, a self-glycosylating protein that initiates the synthesis of new glycogen molecules, could explain these differences in liver glycogen concentration. Glycogenin activity was measured by the incorporation of 14C-glucose from UDP-U-14C-glucose into an acid-precipitable product before and after amylase treatment of liver extracts. The glycogenin activity was similar in normal, diabetic and adrenalectomized fasted animals, regardless of the hepatic glycogen concentration. In fasted rats, glycogenin was present predominantly as the free-form of the enzyme, i.e., not attached to an amylase-digestible glycan, presumably glycogen. In contrast, in fed rats, the majority, if not all of the glycogenin was incorporated into a glycogen-like (proteoglycan) molecule. Proteoglycan synthase activity, previously identified in normal fed rats, also was present in diabetic and adrenalectomized fed rats, and the activity was similar. Thus, the altered ability to store hepatic glycogen in diabetic fed and fasted and adrenalectomized fasted rats cannot be explained by decreases in glycogenin or proteoglycan synthase activities, at least as measured using the present assays.
Assuntos
Adrenalectomia , Diabetes Mellitus Experimental/metabolismo , Glicoproteínas/metabolismo , Fígado/metabolismo , Amilases/química , Amilases/metabolismo , Animais , Autorradiografia , Western Blotting , Jejum , Glucosiltransferases , Glicogênio/metabolismo , Glicoproteínas/análise , Glicoproteínas/imunologia , Masculino , Manganês/química , Manganês/metabolismo , Músculo Esquelético/química , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration. RESEARCH DESIGN AND METHODS: The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700. RESULTS: The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, high-carbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets. CONCLUSIONS: A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Carboidratos da Dieta , Glucagon/sangue , Insulina/sangue , Amido , Idoso , Nitrogênio da Ureia Sanguínea , Diabetes Mellitus Tipo 2/urina , Ingestão de Energia , Ácidos Graxos não Esterificados/sangue , Frutose , Galactose , Glucagon/metabolismo , Glucose , Glicosúria , Humanos , Insulina/metabolismo , Secreção de Insulina , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
OBJECTIVE: To directly compare results obtained using an ion-exchange high-performance liquid chromatography (HPLC) HbA1c method used in the Diabetes Control and Complications Trial with two different affinity chromatography methods in which "total GHb" is determined. RESEARCH DESIGN AND METHODS: Blood was obtained from a large number of people with and without known diabetes. The specimens were divided and assayed for HbA1c and for total GHb. Total GHb was determined using a semi-automated gravity-elution boronate affinity chromatography method and an automated boronate affinity HPLC method. The results obtained with the two methods were also compared. RESULTS: In subjects without known diabetes, the mean percentage HbA1c and the range of values were similar to the total GHb values in the same subjects when assayed using the semi-automated affinity gravity-elution method (mean 5.2 +/- 0.4 and 5.1 +/- 0.4% [SD], respectively). With the affinity HPLC method, results were 5.3 +/- 0.4%. The similarity in results was surprising. However, analysis of the data suggests that a large proportion of the material in the HbA1c fraction measured using this ion-exchange HPLC method is not GHb, as pointed out by others. Although the results were similar in people without known diabetes, in the people with diabetes, the incremental increase was approximately 25% greater for the total GHb when compared with the increase in HbA1c. When corrected for the non-GHb being measured by the HbA1c method, it can be calculated that approximately 40% more GHb is measured using affinity chromatography over the entire range of GHb values. CONCLUSIONS: The similarity in the mean and range of percent HbA1c and in percent total GHb using these different methods can be attributed to two factors: 1) the HbA1c ion-exchange method measures only approximately 50-60% of the total GHb present, and 2) approximately 40-50% of the material being measured in the HbA1c fraction is not GHb, i.e., offsetting factors fortuitously resulted in values similar to the more specific affinity methods. The greater incremental increase in percent total GHb compared with percent HbA1c in people with diabetes can be attributed to the greater amount of GHb being measured with the affinity methods.
Assuntos
Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Hemoglobinas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia de Afinidade/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Discrete-time state-space models were developed to describe contemporaneous responses of plasma insulin and glucose of normal human subjects. Male and female subjects ingested three consecutive identical meals from isocaloric diets classified as high-carbohydrate, high-fat, high-protein, or standard. Distinctly different glucose and insulin responses were measured in men and women. A seven-state system of linear equations, three in insulin and four in glucose, was identified and estimated to describe responses in men. A six-state system, three in insulin and three in glucose, describes responses in women. Model simulations at 15-min intervals closely match measured concentrations over a 12-h period. Effects of diet content and meal timing on insulin and glucose concentrations were quantified. Dynamic insulin and glucose responses to isocaloric meals of pure carbohydrate, fat, and protein diets were projected on the basis of models developed from mixed diets. The symmetry of the projections indicates that positive excursions in glucose concentrations associated with carbohydrate intake may be matched with negative excursions associated with fat and protein intake to help manage postmeal glucose excursions.
Assuntos
Glicemia/metabolismo , Dieta , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Adulto , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Proteínas Alimentares/farmacologia , Ingestão de Energia , Feminino , Humanos , Masculino , Modelos Biológicos , Caracteres SexuaisRESUMO
Glycogen storage disease type 0 (GSD-0) is a rare form of fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia. The glycogen synthase (GS) activity has been low or immeasurable in liver biopsies, whereas the liver glycogen content has been only moderately decreased. To investigate whether mutations in the liver GS gene (GYS2) on chromosome 12p12.2 were involved in GSD-0, we determined the exon-intron structure of the GYS2 gene and examined nine affected children from five families for linkage of GSD-0 to the GYS2 gene. Mutation screening of the 16 GYS2 exons was done by single-strand conformational polymorphism (SSCP) and direct sequencing. Liver GS deficiency was diagnosed from liver biopsies (GS activity and glycogen content). GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content. After suggestive linkage to the GYS2 gene had been established (LOD score = 2.9; P < 0.01), mutation screening revealed several different mutations in these families, including a premature stop codon in exon 5 (Arg246X), a 5'-donor splice site mutation in intron 6 (G+1T--> CT), and missense mutations Asn39Ser, Ala339Pro, His446Asp, Pro479Gln, Ser483Pro, and Met491Arg. Seven of the affected children carried mutations on both alleles. The mutations could not be found in 200 healthy persons. Expression of the mutated enzymes in COS7 cells indicated severely impaired GS activity. In conclusion, the results demonstrate that GSD-0 is caused by different mutations in the GYS2 gene.