5.0.0.0 HY­PO­GLYCEMIA

5.1.0.0 Rec­om­men­da­tions

Rec­om­men­da­tions

6.8 In­di­vid­u­als at risk for hy­po­glycemia should be asked about symp­tomat­ic and asymp­tomat­ic hy­po­glycemia at each en­counter. C

6.9 Glu­cose(15–20 g) is thep­re­ferred treat­ment for the con­scious in­di­vid­u­al with blood glu­cose <70 mg/dL [3.9 mmol/‍L]), al­though any form of car­bo­hy­drate that con­tains glu­cose may be used. Fif­teen min­utes after treat­ment, if SMBG shows con­tin­ued hy­po­glycemia, the treat­ment should be re­peat­ed. Once SMBG re­turns to nor­mal, the in­di­vid­u­al should con­sume a meal or snack to pre­vent re­cur­rence of hy­po­glycemia. E

6.10 Glucagon should be pre­scribed for all in­di­vid­u­als at in­creased risk of level 2 hy­po­glycemia, defined as blood glu­cose <54 mg/dL (3.0 mmol/‍L), so it is avail­able should it be need­ed. Care­givers, school per­son­nel, or fam­i­ly mem­bers of these in­di­vid­u­als should know where it is and when and how to ad­min­is­ter it. Glucagon ad­min­is­tra­tion is not lim­it­ed to health care pro­fes­sion­als. E

6.11 Hy­po­glycemia un­aware­ness or one or more episodes of level 3 hy­po­glycemia should trig­ger ree­va­lua­ti­on of the treat­ment reg­i­men. E

6.12 Insulin-treat­ed pa­tients with hy­po­glycemia un­aware­ness or an episode of level 2 hy­po­glycemia should be ad­vised to raise their glycemic tar­gets to strict­ly avoid hy­po­glycemia for at least sev­er­al weeks in order to par­tial­ly re­verse hy­po­glycemia un­aware­ness and re­duce risk of fu­ture episodes. A

6.13 On­go­ing as­sess­ment of cog­ni­tive func­tion is sug­gested with in­creased vig­i­lance for hy­po­glycemia by the clin­i­cian, pa­tient, and care­givers if low cog­ni­tion or de­clin­ing cog­ni­tion is found. B

Table 6.3—Clas­sification of hy­po­glycemia (44)

Hy­po­glycemia is the major lim­it­ing fac­tor in the glycemic man­age­ment of type 1 and type 2 di­a­betes. Rec­om­men­da­tions re­gard­ing the clas­sification of hy­po­glycemia are out­lined in Table 6.3 (44). Level 1 hy­po­glycemia is defined as a mea­sur­able glu­cose con­cen­tra­tion <70 mg/dL (3.9 mmol/‍L) but ≥54 mg/dL (3.0 mmol/‍L). A blood glu­cose con­cen­tra­tion of 70 mg/dL (3.9 mmol/‍L) has been rec­og­nized as a thresh­old for neu­roen­docrine re­sponses to falling glu­cose in peo­ple with­out di­a­betes. Be­cause many peo­ple with di­a­betes demon­strate im­paired coun­ter­reg­u­la­to­ry re­sponses to hy­po­glycemia and/‍or ex­pe­ri­ence hy­po­glycemia un­aware­ness, a mea­sured glu­cose level <70 mg/dL (3.9 mmol/‍L) is con­sid­ered clin­i­cally im­por­tant, inde­pendent of the sever­i­ty of acute hy­po­glyce­mic symp­toms. Level 2 hy­po­glycemia (defined as a blood glu­cose con­cen­tra­tion <54 mg/dL [3.0 mmol/‍L]) is the thresh­old at which neu­ro­gly­copenic symp­toms begin to occur and re­quires im­me­di­ate ac­tion to re­solve the hy­po­glyce­mic event. Last­ly, level 3 hy­po­glycemia is defined as a se­vere event char­ac­ter­ized by al­tered men­tal and/‍or phys­i­cal func­tioning that re­quires as­sis­tance from an­oth­er per­son for re­cov­ery.

Stud­ies of rates of level 3 hy­po­glycemia that rely on claims data for hos­pi­tal­iza­tion, emer­gen­cy de­part­ment vis­its, and am­bu­lance use sub­stan­tial­ly un­der­es­ti­mate rates of level 3 hy­po­glycemia (45), yet find high bur­den of hy­po­glycemia in adults over 60 years of age in the com­mu­ni­ty (46). African Amer­i­cans are at sub­stan­tial­ly in­creased risk of level 3 hy­po­glycemia (46,47). In ad­di­tion to age and race, other im­por­tant risk fac­tors found in a com­mu­ni­ty-‍based epi­demi­o­log­ic co­hort of older black and white adults with type 2 di­a­betes in­clude in­sulin use, poor or mod­er­ate ver­sus good glycemic con­trol, al­bu­min­uria, and poor cog­ni­tive func­tion (46).

Symp­toms of hy­po­glycemia in­clude, but are not lim­it­ed to, shak­i­ness, ir­ri­tabil­i­ty, con­fu­sion, tachy­car­dia, and hunger. Hy­po­glycemia may be in­con­ve­nient or fright­en­ing to pa­tients with di­a­betes. Level 3 hy­po­glycemia may be rec­og­nized or unrec­og­nized and can progress to loss of con­sciousness, seizure, coma, or death. It is re­versed by ad­min­is­tra­tion of rapid-‍act­ing glu­cose or glucagon. Hy­po­glycemia can cause acute harm to the per­son with di­a­betes or oth­ers, es­pe­cial­ly if it caus­es falls, motor ve­hi­cle ac­ci­dents, or other in­jury. A large co­hort study sug­gested that among older adults with type 2 di­a­betes, a his­to­ry of level 3 hy­po­glycemia was as­so­ci­at­ed with greater risk of de­men­tia (48). Con­verse­ly, in a sub­study of the AC­CORD trial, cog­ni­tive im­pair­ment at base­line or de­cline in cog­ni­tive func­tion dur­ing the trial was significant­ly as­so­ci­at­ed with sub­se­quent episodes of level 3 hy­po­glycemia (49). Ev­i­dence from DCCT/EDIC, which in­volved ado­les­cents and younger adults with type 1 di­a­betes, found no as­so­ci­a­tion be­tween fre­quen­cy of level 3 hy­po­glycemia and cog­ni­tive de­cline (50), as dis­cussed in Sec­tion 13 “Chil­dren and Ado­les­cents.”

Level 3 hy­po­glycemia was as­so­ci­at­ed with mor­tal­i­ty in par­tic­i­pants in both the stan­dard and the in­ten­sive glycemia arms of the AC­CORD trial, but the re­la­tion­ships be­tween hy­po­glycemia, achieved A1C, and treat­ment in­ten­si­ty were not straight-‍for­ward. An as­so­ci­a­tion of level 3 hy­po­glycemia with mor­tal­i­ty was also found in the AD­VANCE trial (51). An as­so­ci­a­tion be­tween self-‍re­port­ed level 3 hy­po­glycemia and 5-year mor­tal­i­ty has also been re­port­ed in clin­i­cal prac­tice (52).

Young chil­dren with type 1 di­a­betes and the el­der­ly, in­clud­ing those with type 1 and type 2 di­a­betes (48,53), are noted as par­tic­u­lar­ly vul­ner­a­ble to hy­po­glycemia be­cause of their re­duced abil­i­ty to rec­og­nize hy­po­glyce­mic symp­toms and ef­fec­tively com­mu­ni­cate their needs. In­di­vid­u­al­ized glu­cose tar­gets, pa­tient ed­u­ca­tion, di­etary in­ter­ven­tion (e.g., bed­time snack to pre­vent overnight hy­po­glycemia when specifically need­ed to treat low blood glu­cose), ex­er­cise man­age­ment, med­i­ca­tion ad­just­ment, glu­cose mon­i­tor­ing, and rou­tine clin­i­cal surveil­lance may im­prove pa­tient out­comes (54). CGM with au­to­mat­ed low glu­cose sus­pend has been shown to be ef­fec­tive in re­duc­ing hy­po­glycemia in type 1 di­a­betes (55). For pa­tients with type 1 di­a­betes with level 3 hy­po­glycemia and hy­po­glycemia un­aware­ness that per­sists de­spite med­i­cal treat­ment, human islet trans­plan­ta­tion may be an op­tion, but the ap­proach re­mains experimen­tal (56,57).

In 2015, the ADA changed its prepran­di­al glycemic tar­get from 70–130 mg/dL (3.9–7.2 mmol/‍L) to 80–130 mg/dL (4.4–7.2 mmol/‍L). This change reflects the re­sults of the ADAG study, which demon­strat­ed that high­er glycemic tar­gets cor­re­spond­ed to A1C goals (7). An ad­di­tional goal of rais­ing the lower range of the glycemic tar­get was to limit overtreat­ment and pro­vide a safe­ty mar­gin in pa­tients titrat­ing glu­cose-‍low­er­ing drugs such as in­sulin to glycemic tar­gets.