David Goldblatt

Decreased insulin sensitivity of forearm muscle in myotonic dystrophy.

Previous studies of patients with myotonic dystrophy have demonstrated hyperinsulinism after glucose loading. This hyperinsulinism has been attributed by some investigators to tissue insulin resistance. We have directly studied insulin sensitivity of forearm muscle in patients having such hyperinsulinism. The effect of an intrabrachial arterial insulin infusion (100 mu U/kg per min) on glucose uptake was determined in six cases of myotonic dystrophy, six normal subjects, and in seven disease control subjects with myotonia or wasting from other disorders. There was no significant difference in insulin tolerance comparing myotonic dystrophy patients to the normal and disease control groups. Glucose tolerance and basal insulin levels were normal in the myotonic dystrophy patients, but hyperinsulinism occurred after glucose ingestion. After 25 min of intra-arterial insulin, the mean peak muscle glucose uptake in myotonic dystrophy was 2.54 +/- 0.54 mu mol/min per 100 ml forearm compared to 5.24 +/- 0.86 mu mol/min per 100 ml for disease controls (P is less than 0.05). Myotonic dystrophy patients showed a peak glucose uptake increment of only 2.6 +/- 0.2-fold over basal contrasted with the disease control value of 6.5 +/- 1.0-fold (P is less than 0.02) and the normal control value of 8.8 +/- 1.1-fold (P is less than 0.01). Thus, there was an absolute as well as a relative decrease in muscle insulin sensitivity in myotonic dystrophy patients compared to both control groups. The peak increments in arterio-superficial venous glucose concentration differences after insulin infusion were not significantly different comparing myotonic dystrophy and control groups. These data suggest that in myotonic dystrophy, there is insulin insensitivity of skeletal muscle.

Muscle insulin resistance in myotonic dystrophy Effect of supraphysiologic insulinization

In myotonic dystrophy, there is resistance of forearm muscle to physiologic concentrations of insulin. To determine whether this resistance is due to a shift in the dose-response curve resulting from decreased numbers of insulin receptors, we measured the effects of supraphysiologic insulinization (200 μU per kilogram per minute) on the uptake of glucose by forearm muscle in three patients with myotonic dystrophy and five denervated patients with comparable wasting. Although insulin levels were higher in patients with myotonic dystrophy than in controls, peak glucose uptake remained significantly lower in myotonic dystrophy patients. The findings are consistent with a postinsulin receptor defect of muscle and with altered membrane function in myotonic dystrophy.

SPINAL GANGLION INVOLVEMENT IN EXPERIMENTAL POLIOMYELITIS.

IT IS characteristic of neurotropic viruses that they attack the nervous system in a selective manner, so that some neuronal centers are frequently or severely affected while other centers are relatively spared. This characteristic, which can be called differential neuronotropism, is usually evaluated on the basis of histopathological observations and, less securely, by clinical examination in nonfatal human illnesses. The present study was conceived as an attempt to investigate the mechanism of differential neuronotropism by studying one selected example of this phenomenon. It was hypothesized that there are several requirements for definite and permanent functional impairment of a neuronal center: (1) virus has reached the affected center, ( 2 ) virus has multiplied in neurons of the center, ( 3 ) virus multiplication destroys at least some infected neurons, and (4) the proportion of neuronal population destroyed is sufficiently great. Conversely, it was postulated that a neuronal center will show functional sparing if any one of these requirements is not met. In the present study, a single center, the spinal ganglion, was selected as a model to analyze the mechanism of neuronal sparing in experimental poliomyelitis, although it was recognized that different mechanisms might apply to other centers which are usually unaffected by the disease. For purposes of comparison, the anterior horn of the spinal cord was selected as a center prone to severe functional involvement in poliomyelitis. Evidence for sparing of the spinal ganglion in poliomyelitis is both clinical and pathological. Clinical observations have the advantage